Publisher: Elsevier   (Total: 3161 journals)

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Showing 1 - 200 of 3161 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 39, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 26, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 106, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 28, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 43, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 7)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6)
Acta Astronautica     Hybrid Journal   (Followers: 446, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 30, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 3)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 11, SJR: 0.18, CiteScore: 1)
Acta Histochemica     Hybrid Journal   (Followers: 5, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 322, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2, SJR: 1.793, CiteScore: 6)
Acta Psychologica     Hybrid Journal   (Followers: 26, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access   (Followers: 1)
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 7, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 8)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 18, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 9, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 13, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 188, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 13, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 17, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 30, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 12, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 12, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 24, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 15, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 1, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 35, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 5)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 14)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 29, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 11, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 11, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 21, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 16)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 14)
Advances in Digestive Medicine     Open Access   (Followers: 13)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Drug Research     Full-text available via subscription   (Followers: 26)
Advances in Ecological Research     Full-text available via subscription   (Followers: 45, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 30, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 9)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 52, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 2)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 68, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 21, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 12, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 8, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 26, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 26)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 3, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 37, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 9, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 21, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 17, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 9, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 26)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 5)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 18, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 6, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 27, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 19)
Advances in Pharmacology     Full-text available via subscription   (Followers: 17, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 11)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 6)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 69)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 7, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (Followers: 3, SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 7)
Advances in Space Research     Full-text available via subscription   (Followers: 430, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 6)
Advances in Surgery     Full-text available via subscription   (Followers: 13, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 37, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 20)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 6, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 56, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 394, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 12, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 487, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 18, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 32, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 46, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 58, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 8, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 12, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 12)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 2, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 11, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 55, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 6, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 6, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 58, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 67, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 48, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 13)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 15, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 39, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 29, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 37, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 50)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 264, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 67, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 32, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 30, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 39, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 7)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 67, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 25, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription   (Followers: 1)
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 6, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 44, SJR: 1.512, CiteScore: 5)
Analytica Chimica Acta : X     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 214, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 13, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 14)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 25, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)
Animal Behaviour     Hybrid Journal   (Followers: 236, SJR: 1.58, CiteScore: 3)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 7, SJR: 0.937, CiteScore: 2)
Animal Reproduction Science     Hybrid Journal   (Followers: 7, SJR: 0.704, CiteScore: 2)
Annales d'Endocrinologie     Full-text available via subscription   (Followers: 3, SJR: 0.451, CiteScore: 1)

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Similar Journals
Journal Cover
Nanomedicine: Nanotechnology, Biology and Medicine
Journal Prestige (SJR): 1.743
Citation Impact (citeScore): 6
Number of Followers: 7  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1549-9634
Published by Elsevier Homepage  [3161 journals]
  • Doxil chemotherapy plus liposomal P5 immunotherapy decreased
           myeloid-derived suppressor cells in murine model of breast cancer
    • Abstract: Publication date: Available online 10 January 2020Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Jamshid Gholizadeh Navashenaq, Parvin Zamani, Amin Reza Nikpoor, Jalil Tavakkol-Afshari, Mahmoud Reza JaafariAbstractMyeloid-derived suppressor cells (MDSCs) play a pivotal role in cancer. To overcome the problem of the MDSCs in the tumor microenvironment in this study, a combination of immunotherapy and chemotherapy was used. For this purpose, a liposomal formulation of P5 peptide and PEGylated liposomal doxorubicin (Doxil®) was utilized to treat mice bearing HER2+ tumor model. The results revealed that Doxil® administration before immunotherapy had not only reduced the population and functions of the MDSCs in the spleen (P 
       
  • Novel therapeutic strategies for Alzheimer's disease: Implications from
           cell-based therapy and Nanotherapy
    • Abstract: Publication date: Available online 10 January 2020Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Hossein Derakhshankhah, Soraya Sajadimajd, Samira Jafari, Zhila Izadi, Sajad Sarvari, Majid Sharifi, Mojtaba Falahati, Faezeh Moakedi, Willis Collins Akeyo Muganda, Mareike Müller, Mohammad Raoufi, John F. PresleyAbstractAlzheimer's disease (AD) is a multifactorial neurodegenerative disease which leads to progressive dysfunction of cognition, memory and learning in elderly people. Common therapeutic agents are not only inadequate to suppress the progression of AD pathogenesis but also produce deleterious side effects; hence development of alternative therapies is required to specifically suppress complications of AD. The current review provides a commentary on conventional as well as novel therapeutic approaches with an emphasis on stem cell and nano-based therapies for improvement and management of AD pathogenesis. According to our overview of the current literature, AD is a multi-factorial disorder with various pathogenic trajectories hence a multifunctional strategy to create effective neuroprotective agents is required to treat this disorder.Graphical AbstractAlzheimer disease is a multifactorial disorder, which its management and treatment requires combinational strategies for design an effective neuroprotective agent.Unlabelled Image
       
  • A comparative study of the effect of drug hydrophobicity on nanoparticle
           drug delivery in vivo using two photosensitizers
    • Abstract: Publication date: Available online 10 January 2020Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Jihwan Son, Donghyun Lee, Jihye Yoo, Changhee Park, Heebeom KooAbstractTo evaluate the effect of drug hydrophobicity on nanoparticle delivery in vivo, we conducted a comparative study using different photosensitizer-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Chlorin e6 (Ce6) and pheophorbide a (Pba) with similar structure but different hydrophobicity were loaded into PLGA-NPs separately. We observed release profiles and photodynamic effects in vitro from the resulting Ce6- and Pba-PLGA-NPs. After intravenous injection into SCC7 tumor-bearing mice, biodistribution and accumulation of two drugs in tumor tissue were observed by real-time fluorescence imaging. Finally, in vivo photodynamic therapy with Ce6- and Pba-PLGA-NPs provided different therapeutic results according to imaging data. The results demonstrated that drug hydrophobicity is an important factor in nanoparticle drug delivery and should be considered for efficient drug delivery in vivo.Graphical AbstractThe purpose of this study was to evaluate the effect of drug hydrophobicity on nanoparticle delivery in vivo. we conducted a comparative study using different photosensitizer-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Chlorin e6 (Ce6) and pheophorbide a (Pba) with similar structure but different hydrophobicity were loaded into PLGA-NPs separately. After intravenous injection into SCC7 tumor-bearing mice, biodistribution and accumulation of two drugs in tumor tissue were observed by real-time fluorescence imaging. Finally, in vivo photodynamic therapy with Ce6- and Pba-PLGA-NPs provided different therapeutic results according to imaging data. The results demonstrated that drug hydrophobicity is an important factor in nanoparticle drug delivery and should be considered for efficient drug delivery in vivo.Unlabelled Image
       
  • Enhanced Neuronal Differentiation of Neural Stem Cells with Mechanically
           Enhanced Touch-Spun Nanofibrous Scaffolds
    • Abstract: Publication date: Available online 10 January 2020Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Darya Asheghali, Se-Jun Lee, Andreas Furchner, Alexey Gruzd, Steven Larson, Alexander Tokarev, Seth Stake, Xuan Zhou, Karsten Hinrichs, Lijie G. Zhang, Sergiy MinkoAbstractWe studied NE-4C neural cells differentiation on 2D polycaprolactone (PCL) nanofibrous scaffolds with systematically varied mechanical characteristics of nanofibers while retaining an unchanged fiber alignment, diameter, and chemical composition. Our experiments demonstrated that the nanofibers with enhanced mechanical properties are beneficial for the preferential development of neuronal cells vs. glial cells. Electrospun (ES) and touch-spun (TS) nanofibers were fabricated with Young’s modulus in the range of 10 MPa to 230 MPa and a fraction of crystallinity from 30% to 80%. The TS fibers undergo a greater drawing ratio and thus approach a greater polymer chain stretching and alignment that resulted in an increased crystallinity. The TS scaffolds demonstrated improved stability in the aqueous cell culture environment, resisting misalignment and entanglement after a period of 2 weeks of swelling followed by 14 days of neural differentiation. The results confirmed that the neurites on the TS fibers have a preferred orientation even after swelling.Graphical AbstractWe analyzed the effect of the mechanical properties of the fibrous scaffolds on the neural stem cell differentiation. Two fiber spinning methods, electro-spinning and touch-spinning, were used to fabricate polycaprolactone fibrous scaffolds with different mechanical properties. We showed enhanced neuronal differentiation of neural stem cells on the mechanically enhanced touch-spun fibers as well as preferential orientation of neurites along the fibers even after swelling.Unlabelled Image
       
  • Ionizing radiation attracts tumor targeting and apoptosis by radiotropic
           lysyl oxidase traceable nanoparticles
    • Abstract: Publication date: February 2020Source: Nanomedicine: Nanotechnology, Biology and Medicine, Volume 24Author(s): Wheemoon Cho, Min Sup Kim, Kee-Ho Lee, Sang Jun Park, Hyun-Jin Shin, Yong Jin Lee, Sang Bum Kim, Youngsook Son, Chun-Ho KimAbstractLysyl oxidase (LOX) is a cell-secreted amine oxidase that crosslinks collagen and elastin in extracellular microenvironment. LOX-traceable nanoparticles (LOXab-NPs) consisting of LOX antibodies (LOXab) and paclitaxel, can accumulate at high concentrations at radiation-treated target sites, as a tumor-targeting drug carrier for chemotherapy. Tumor-targeting and anticancer effects of PLGA based LOXab-NPs in vitro and in vivo were evaluated at radiation-targeted site. In the in vivo A549 lung carcinoma xenograft model, we showed highly specific tumor targeting (above 7.0 times higher) of LOXab-NPs on irradiated tumors. Notably, systemically administered NPs delayed tumor growth, reducing tumor volumes by more than 2 times compared with non-irradiated groups (222% vs.>500%) over 2 weeks. Radiotropic LOXab-NPs can serve as chemotherapeutic vehicles for combined targeted chemo-radiotherapy in clinical oncology.Graphical AbstractLOX-traceable PLGA based nanoparticles consisting of LOX antibodies and paclitaxel (LOX-NPs(P)), which can accumulate at high concentrations at radiation-treated target sites, as a tumor-targeting drug carrier for chemotherapy. Biodistribution of NPs on extracted organs from sacrificed mice after 7 days. Photograph of organs (Heart, Liver, Spleen, lung, kidney, 10 Gy irradiated A549 tumor and non-irradiated tumor). Ex vivo images of organs administrated nanoparticles after 7 days. Photographs of extracted A549 tumor from animal euthanasia. IR (−) indicated non-irradiated (only drugs series administration) groups. Control group administrated only saline.Unlabelled Image
       
  • Bioreducible crosslinked cationic nanopolyplexes from clickable
           polyethylenimines enabling robust cancer gene therapy
    • Abstract: Publication date: February 2020Source: Nanomedicine: Nanotechnology, Biology and Medicine, Volume 24Author(s): Kangkang An, Huizhi Fengyan, Xinting Xu, Rong Jin, Xiaoxin Hu, Peng Zhao, Chao LinAbstractBioreducible crosslinked polyplexes from branched polyethylenimine (BPEI, 10 kDa) were successfully constructed through DNA neutralization by disulfide-linked azidated BPEI (PAZ) and subsequent DNA condensation by azadibenzocyclooctyne-modified BPEI (PDB), following their self-crosslinking via azide-azadibenzocyclooctyne click chemistry. Click-crosslinked cationic polyplexes (c-polyplexes) revealed high extracellular colloidal stability against negative heparin and ions while intracellular bioreducible degradability for efficient gene unpacking. In vitro gene transfection in cancer cells indicated that the c-polyplexes produced markedly higher transfection efficiency than non-crosslinked counterparts in the serum. The c-polyplexes also had prolonged circulation kinetics, elevated gene accumulation level in SKOV-3 tumor xenografted in a mouse model and in turn superior transgene expression in the tumor. By small hairpin RNA for VEGF silencing, the c-polyplexes exerted significant tumor growth inhibition following with low systemic toxicity in the mouse. This study highlights the design of clickable polycations to construct crosslinked cationic nanopolyplexes for intravenous gene delivery against cancer.Graphical AbstractBinary crosslinked cationic polyplexes from clickable polyethylenimines can be easily constructed via azadibenzocyclooctyne-azide click chemistry for robust cancer gene therapy.Unlabelled Image
       
  • Superior temperature sensing of small-sized upconversion nanocrystals for
           simultaneous bioimaging and enhanced synergetic therapy
    • Abstract: Publication date: February 2020Source: Nanomedicine: Nanotechnology, Biology and Medicine, Volume 24Author(s): Guofeng Liu, Fan Jiang, Yeqing Chen, Chang Yu, Binbin Ding, Shuai Shao, Mochen Jia, Ping'an Ma, Zuoling Fu, Jun LinThe upconversion nanoparticles (UCNPs) exhibit versatility applications aiming at biological domains for decades on account of superior optical characteristics. Nevertheless, the UCNPs are confronted with tremendous difficulties in biological field owing to large grain size, low fluorescence efficiency, and single function. Herein, the small-sized CaF2: Yb3+/Er3+ UCNPs coated with NaGdF4 shells (activator and inert, UCNPs-RBHA-Pt-PEG) not only burst out strong fluorescence, but also provide prominent diagnosability by taking advantage of magnetic resonance (MR) imaging as well as temperature sensing and inhibiting capability for CT26 tumor tissues based on synergetic therapy modality of photodynamic therapy (PDT) and chemotherapy. Ultimately, the tumor sizes decrease visibly after injected with UCNPs-RBHA-Pt-PEG and simultaneously irradiated with near infrared (NIR) light at low power density (0.35 W/cm2, 6 min). In summary, the small-sized and strong-fluorescent single nanoparticles with multi-functions may provide a valuable enlightenment for diagnosis and treatment of cancer in the future.Graphical abstractThe small-sized and enhanced-fluorescent CaF2 UCNPs emit strong fluorescence after coated with NaGdF4 shells (activator and inert). The ample PDT efficacy is achieved relied on the fluorescence resonance energy transfer owing to a large overlap between upconversion emission and rose-bengal hexanic acid absorption (UCNPs-RBHA). At the same time, the UCNPs-RBHA conjugated with platinum (IV) and polyethylene glycol possesses high cell apoptosis for the CT26 cells due to high endocytosis. The UCL and MR imaging, temperature sensing, and strong antitumor effect based on the synergetic therapy of PDT and chemotherapy are achieved on the single nanoparticles.Unlabelled Image
       
  • Biomimetic nanovesicles made from iPS cell-derived mesenchymal stem cells
           for targeted therapy of triple-negative breast cancer
    • Abstract: Publication date: Available online 27 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Qingguo Zhao, Bo Hai, Xiao Zhang, Jing Xu, Brian Koehler, Fei LiuAbstractNanoparticles made from membrane of mesenchymal stem cells (MSCs) showed active targeting capacities to prostate and lung cancers, but further studies are hindered by limited expandability and donor variations of tissue-derived MSCs. We have derived MSCs with an unlimited supply and uniform homing capacity to triple-negative breast cancer (TNBC) from human induced pluripotent stem cells (iPSCs). By breaking down intact iPSC-MSCs, we efficiently developed nanovesicles that selectively accumulated in primary and metastatic TNBC after systemic infusion in mouse models. When loaded with a chemotherapeutic drug doxorubicin, iPSC-MSC nanovesicles showed superior cytotoxic effects on doxorubicin-resistant TNBC cells, and significantly decreased the incidence and burden of metastases in mouse models of spontaneous and experimental metastatic TNBC compared with free or liposomal doxorubicin. These nanovesicles showed no detectable immunogenicity or toxicity, and are stable after storage. Our data indicate that iPSC-MSC nanovesicles are promising to improve TNBC treatment as a standardized targeting platform.Graphical AbstractMesenchymal stem cells derived from induced pluripotent cells (iPSC-MSCs) stably express multiple membrane proteins targeting triple-negative breast cancer (TNBC). We developed nanovesicles mimicking extracellular vesicles from iPSC-MSCs with a much higher yield by serial extrusion. Systemically infused nanovesicles selectively accumulated in mouse primary and metastatic TNBC as indicated by imaging membrane dye DiR and cytoplasmic transgene luciferase (rLuc). Doxorubicin (Dox) was efficiently loaded into nanovesicles during extrusion and efficiently delivered by nanovesicles into TNBC, which effectively decreased the incidence and burden of metastasis. The selectively uptake of nanovesicles by TNBC cells is likely through both receptor-mediated endocytosis and enhanced macropinocytosis.Unlabelled Image
       
  • Nanoparticle reinforced bacterial outer-membrane vesicles effectively
           prevent fatal infection of carbapenem-resistant Klebsiella pneumonia
    • Abstract: Publication date: Available online 27 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Guangxi Wu, Haiying Ji, Xiaoyu Guo, Yongyong Li, Tianbin Ren, Haiqing Dong, Jingxian Liu, Yiqiong Liu, Xueyin Shi, Bin HeAbstractInfection resulting from carbapenem-resistant Klebsiella pneumoniae (CRKP) is an intractable clinical problem. Outer membrane vesicles (OMVs) from CRKP are believed to be potential vaccine candidates. However, their immune response remains elusive due to low structural stability and poor size homogeneity. In this study, hollow OMVs were reinforced internally by size-controlled BSA nanoparticles to obtain uniform and stable vaccines through hydrophobic interaction. The result showed that the BSA-OMV nanoparticles (BN-OMVs) were homogenous with a size around 100 nm and exhibited a core-shell structure. Remarkably, subcutaneous BN-OMVs vaccination mediated significantly higher CRKP specific antibody titers. The survival rate of the mice infected with a lethal dose of CRKP was increased significantly after BN-OMV immunization. The adoptive transfer experiment demonstrated that the protective effect of BN-OMVs was dependent on humoral and cellular immunity. This study demonstrated that the structure optimization improved the immune efficacy of OMVs for vaccine development against CRKP.Graphical AbstractTo synthesize BN, BSA molecules were first treated with DTT. Subsequently, SDS and MES were carefully added into the reduced BSA solution. After homogenous dispersion, the assembly process was performed in water bath at 65 oC under rigorous stirring (750 rpm). The BSA molecules were then assembled into NPs. The bacterial outer-membrane was collected in the form of outer membrane vesicles (OMVs) and then mixed with BNs with a diameter of approximately 70 nm. Through an extrusion process, the bacterial outer-membrane was coated with BN and translocated onto the BN surfaces to form bacterial outer-membrane-coated BN.Unlabelled Image
       
  • Mycophenolate co-administration with quercetin via lipid-polymer hybrid
           nanoparticles for enhanced breast cancer management
    • Abstract: Publication date: Available online 26 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Gopal Patel, Neeraj Singh Thakur, Varun Kushwah, Mahesh D Patil, Shivraj Hariram Nile, Sanyog Jain, Guoyin Kai, Uttam Chand BanerjeeAbstractMycophenolic acid (MPA) having promising anticancer properties, however, it has limited clinical applications in vivo due to hydrophobic nature, high first-pass metabolism, lack of targeting, etc. These associated problems could be addressed by developing a suitable delivery vehicle, inhibiting the first-pass metabolism and additive/synergistic pharmacodynamic effect. Thus, MPA loaded highly stable lipid polymer hybrid nanoparticles (LPNs) were developed and investigated with the combination of quercetin (QC); a CYP 450 inhibitor cum anticancer. LPNs of MPA and QC (size; 136.11 ± 12.4 and 176 ± 34.65 nm, respectively) demonstrated higher cellular uptake and cytotoxicity of combination therapy (MPA-LPN + QC-LPN) compared to individual congeners in MCF-7 cells. In vivo pharmacokinetics demonstrated 2.17 fold higher T1/2 value and significantly higher pharmacodynamic activity in case of combination therapy compared to free MPA. In nutshell, the combinatory therapeutic regimen of MPA and QC could be a promising approach in improved breast cancer management.Graphical AbstractCo-administration of quercetin (a CYP450 inhibitor) with mycophenolate have demonstrated reduced first pass metabolism with significant increase in bioavailability of mycophenolic acid and its anticancer efficacy in breast tumor bearing SD rats. Moreover, the inherent anticancer property of quercetin enhances the cytotoxic effect of mycophenolic acid synergistically.Unlabelled Image
       
  • Advances in dual functional antimicrobial and osteoinductive biomaterials
           for orthopaedic applications
    • Abstract: Publication date: Available online 18 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Samson Afewerki, Nicole Bassous, Samarah Harb, Carlos Palo-Nieto, Guillermo U. Ruiz-Esparza, Fernanda R. Marciano, Thomas J. Webster, André Sales Aguiar Furtado, Anderson O. LoboAbstractA vast growing problem in orthopaedic medicine is the increase of clinical cases with antibiotic resistant pathogenic microbes, which is predicted to cause higher mortality than all cancers combined by 2050. Bone infectious diseases limit the healing ability of tissues and increase the risk of future injuries due to pathologic tissue remodelling. The traditional treatment for bone infections has several drawbacks and limitations, such as lengthy antibiotic treatment, extensive surgical interventions, and removal of orthopaedic implants and/or prosthesis, all of these resulting in long-term rehabilitation. This is a huge burden to the public health system resulting in increased healthcare costs. Current technologies e.g. co-delivery systems, where antibacterial and osteoinductive agents are delivered encounter challenges such as site-specific delivery, sustained and prolonged release, and biocompatibility. In this review, these aspects are highlighted to promote the invention of the next generation biomaterials to prevent and/or treat bone infections and promote tissue regeneration.Graphical AbstractDual functional biomaterials with the ability of being antimicrobial and simultaneously osteoinductive are highly desirable and can potentially solve grand challenges in various orthopaedic applications. In this review, we highlight recent advances for the next generation of biomaterials preventing/treating bone infections and promoting tissue growth. We discuss some fundamental aspects which hopefully will pave the way for the invention of novel and innovative biomaterials.Unlabelled Image
       
  • Encapsulated bacteriophages in alginate-nanohydroxyapatite hydrogel as a
           
    • Abstract: Publication date: Available online 17 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): J Barros, LDR Melo, RA Silva, MP Ferraz, J Azeredo, V Pinheiro, B Colaço, MH Fernandes, PS Gomes, FJ MonteiroAn innovative delivery system based on bacteriophages-loaded alginate-nanohydroxyapatite hydrogel was developed as a multifunctional approach for local tissue regeneration and infection prevention and control. Bacteriophages were efficiently encapsulated, without jeopardizing phage viability and functionality, nor affecting hydrogel morphology and chemical composition. Bacteriophage delivery occurred by swelling-disintegration-degradation process of the alginate structure and was influenced by environmental pH. Good tissue response was observed following the implantation of bacteriophages-loaded hydrogels, sustaining their biosafety profile. Bacteriophages-loaded hydrogels did not affect osteoblastic cells' proliferation and morphology. A strong osteogenic and mineralization response was promoted through the implantation of hydrogels system with nanohydroxyapatite. Lastly, bacteriophages-loaded hydrogel showed excellent antimicrobial activity inhibiting the attachment and colonization of multidrug-resistant E. faecalis surrounding and within femoral tissues. This new local delivery approach could be a promising approach to prevent and control bacterial contamination during implantation and bone integration.Graphical abstractAn innovative delivery system based on bacteriophages-loaded alginate-nanohydroxyapatite hydrogel was developed as a multifunctional approach to prevent and control bacterial contamination, given the local delivery of phages and their ability to replicate at the site of infection, during the implantation and bone integration, promoted by nanoHA particles.Unlabelled Image
       
  • Balanced Th1/Th2 immune response induced by a MSP1a functional motif
           coupled to multiwalled carbon nanotubes as anti-anaplasmosis vaccine in
           murine model
    • Abstract: Publication date: Available online 16 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Leticia Santos Pimentel, Carolina Alvarenga Turini, Paula Souza Santos, Mariana Abilio de Morais, Aline Gomes Souza, Mariana Botelho Barbosa, Estefânia Mara do Nascimento Martins, Loyane Bertagnolli Coutinho, Clascídia Aparecida Furtado, Luiz Orlando Ladeira, João Ricardo Martins, Luiz Ricardo Goulart, Paula Cristina Batista de FariaAbstractAnaplasmosis is one of the most prevalent tick-borne diseases of cattle caused by Anaplasma marginale. MSP1a surface protein has been shown to be involved in eliciting immunity to infected cattle. Carbon nanotubes (CNTs) has been increasingly highlighted due to their needle like structure, which contain multiple attachment sites for biomolecules and may interact with or cross biological membranes, increasing antigen availability to immune system. Here, we have successfully designed a nanocomplex of a synthetic peptide noncovalently attached to multiwalled CNT (MWCNT). Peptide comprising the core motif of the MSP1a was efficiently adsorb onto the nanoparticle surface. The MWCNT-Am1 nanocomplex exhibited high stability and good dispersibility and in vivo immunization showed high levels of IgG1 and IgG2a, followed by increased expression of pro-inflammatory and anti-inflammatory cytokines. This is a proof-of-concept of a nanovaccine that was able to generate a strong immune response compared to the common antigen-adjuvant vaccine without the nanoparticles.Graphical AbstractWe successfully developed a nanovaccine against bovine anaplasmosis based on the noncovalent attachment of a synthetic peptide (Am1) containing a critical motif sequence of the MSP1a surface protein of Anaplasma marginale to oxidized MWCNTs (multiwalled carbon nanotubes). The reduced length and high stability of the nanocomplex allowed a potent and highly stable balanced Th1/Th2 immune response showing an equivalent level of antibody and better cell-mediated immune responses in mice, compared to the conventional immunization with antigen-adjuvant without nanoparticles.Unlabelled Image
       
  • Photomagnetic Prussian blue nanocubes: Synthesis, characterization, and
           biomedical applications
    • Abstract: Publication date: Available online 15 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Diego S. Dumani, Jason R. Cook, Kelsey P. Kubelick, Jeffrey J. Luci, Stanislav Y. EmelianovAbstractNanoparticles play an important role in biomedicine. We have developed a method for size-controlled synthesis of photomagnetic Prussian blue nanocubes (PBNCs) using superparamagnetic iron oxide nanoparticles (SPIONs) as precursors. The developed PBNCs have magnetic and optical properties desired in many biomedical diagnostic and therapeutic applications. Specifically, the size-tunable photomagnetic PBNCs exhibit high magnetic saturation, strong optical absorption with a peak at approximately 700 nm, and superior photostability. Our studies demonstrate that PBNCs can be used as MRI and photoacoustic imaging contrast agents in vivo. We also showed the utility of PBNCs for labeling and magnetic manipulation of cells. Dual magnetic and optical properties, together with excellent biocompatibility, render PBNCs an attractive contrast agent for both diagnostic and therapeutic applications. The use SPIONs as precursors for PBNCs provides flexibility and allows researchers to design theranostic agents according to required particle size, optical, and magnetic properties.Graphical AbstractA method for the synthesis of photomagnetic Prussian blue nanoparticles is presented. Unlike other synthesis schemes, Prussian blue nanocubes are herein synthesized using iron oxide nanoparticles, which allows for tunable size control and enhanced magnetism. Various biomedical applications are explored including MRI, photoacoustic imaging, and magnetic manipulation for cell screening and delivery.Unlabelled Image
       
  • Silver-based antibacterial strategies for healthcare-associated
           infections: Processes, challenges, and regulations. An integrated review
    • Abstract: Publication date: Available online 14 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Linda Bonilla-Gameros, Pascale Chevallier, Andranik Sarkissian, Diego MantovaniAbstractHealthcare-associated infections (HCAIs) are a major cause of morbidity and mortality worldwide. One of the main routes of transmission is by contact with contaminated surfaces, where nosocomial pathogens form sessile communities called biofilms. When forming biofilms, these pathogens are extremely resistant to antibiotics and standard cleaning procedures. In this regard, in order to eliminate the extent of biofilm formation on these surfaces, intensive efforts have been deployed, particularly in recent years, to develop new antibacterial surfaces containing silver or silver compounds, which can be used to prevent the formation of biofilm. In this review, recent developments in the design and manufacturing of silver-based antibacterial surfaces are described in detail. Up-to-date toxicity and governmental regulations are then extensively presented. Finally, based on current research in this promising field, the main challenges and perspectives for their effective implementation are discussed.Graphical AbstractDuring the last five years, the urgency of identifying more effective antibacterial agents, along with alternatives way to deliver them, has become a central topic of research. In this sense, silver-based antibacterial coatings have been actively studied, making them a valuable option in the treatment of antibacterial surfaces. However, the use of silver nanotechnology in the antimicrobial field is still at pre-clinical or academic research level. In this context, this work highlights the state-of-the-art technology of silver-based antibacterial coatings, including the recent approaches aimed at controlling and characterizing the release of silver and its toxicity.Unlabelled Image
       
  • MKC-Quatsomes: a stable nanovesicle platform for bio-imaging and
           drug-delivery applications
    • Abstract: Publication date: Available online 13 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Guillem Vargas-Nadal, Monica Muñoz-Ubeda, Patricia Alamo, Montserrat Mitjans Arnal, Virtudes Céspedes, Mariana Köber, Elisabet Gonzalez, Lidia Ferrer-Tasies, M Pilar Vinardell, Ramón Mangues, Jaume Veciana, Nora VentosaAbstractQuatsomes are outstanding new lipid-based nanovesicles that are highly homogeneous and stable in different media for years, but the composition must be carefully chosen to avoid any potentially toxic side effects in in vivo applications. To this end, we have developed and studied a novel type of Quatsomes composed of cholesterol and myristalkonium chloride (MKC), the latter being extensively used as antimicrobial preservative in many ophthalmic and parenteral formulations on the EU and USA market. We have synthesized these novel MKC-Quatsomes in different media that are suitable for parenteral administration, and confirmed their stability in these media for 18 months, as well as the stability in human serum for 24 hours. Biodistribution assays were performed after intravenous injection of fluorescently labeled MKC-Quatsomes in live mice bearing xenografted colorectal tumors, showing nanovesicle accumulation in tumors, liver, spleen, and kidneys. No histological alteration or toxicity was observed in any of these organs.Graphical AbstractNew lipid-based nanovesicles composed of myristalkonium chloride (MKC) and cholesterol have been developed and labeled with a fluorescent dye for biodistribution studies. These vesicles, called MKC-Quatsomes, are stable in human serum and have not produced any histological alterations after injection in mice.Unlabelled Image
       
  • Finding the perfect match between nanoparticles and microfluidics to
           respond to cancer challenges
    • Abstract: Publication date: Available online 13 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): F. Raquel Maia, Rui L. Reis, Joaquim M. OliveiraAbstractThe clinical translation of new cancer theranostic has been delayed by inherent cancer’s heterogeneity. Additionally, this delay has been enhanced by the lack of an appropriate in vitro model, capable to produce accurate data. Nanoparticles and microfluidic devices have been used to obtain new and more efficient strategies to tackle cancer challenges. On one hand, nanoparticles-based therapeutics can be modified to target specific cells, and/or molecules, and/or modified with drugs, releasing them over time. On the other hand, microfluidic devices allow the exhibition of physiologically complex systems, incorporation of controlled flow, and control of the chemical environment. Herein, we review the use of nanoparticles and microfluidic devices to address different cancer challenges, such as detection of CTCs and biomarkers, point-of-care devices for early diagnosis and improvement of therapies. The future perspectives of cancer challenges are also addressed herein.Graphical AbstractThe translation of new approaches for cancer theranostic has been delayed. One of the reasons behind it is the lack of an in vitro model capable to produce accurate data. In this reasoning, microfluidic devices and nanoparticles have been pursued to develop new and improved strategies to face different cancer challenges. This document overviews the recent reports that encompass new strategies for the detection of CTCs and biomarkers, for the development of point-of-care devices for early diagnosis, and for the improvement of therapies.Unlabelled Image
       
  • Topical nano-encapsulated cyclosporine formulation for atopic dermatitis
           treatment
    • Abstract: Publication date: Available online 10 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): A. Badihi, M. Frušić-Zlotkin, Y. Soroka, S. Benhamron, T. Tzur, T. Nassar, S. BenitaSystemic cyclosporine A (CsA) therapy shows efficacy in the treatment of recalcitrant severe atopic dermatitis (AD) but elicits severe side-effects. Thus, a topical formulation of CsA nanocapsules (NCs), able to potentially bypass these drawbacks, was developed. CsA-NCs were shown to enhance drug penetration into the various layers of porcine ear skin. Furthermore, the encapsulated CsA was biologically active, as shown in vitro on mouse splenocytes, reflected by inhibition of both cell proliferation and of interleukin (IL)-2 secretion. Ex-vivo efficacy was demonstrated on human skin organ culture by markedly reducing pro-inflammatory cytokines secretion. Finally, CsA-NCs topical formulation elicited improved efficacy in terms of better preservation of the skin barrier integrity, a decrease of the systemic pro-inflammation markers and reduced skin inflammation. The overall results suggest that this original topical platform may provide a novel therapeutic tool of clinical significance compared to the existing topical therapeutic drugs in AD.Graphical Adequate experimental conditions were identified for the formulation of stable nanocapsules of cyclosporine A. The dermal penetration of CsA evaluated on pig skin, showed high drug levels in epidermis and dermis. LPS-induced inflammation in human skin specimens exhibited high levels of IL-6 and IL-8, as well as with blank NCs, whereas 15 μg/cm2 CsA NCs elicited significant reduction of both cytokines' levels, evidencing the release of CsA within the skin. Finally, an in vivo study of OVA-induced AD showed that CsA NCs elicited the most effective results compared to CsA ointment, and other commercial products. (i.e. Graphical abstract: Figures 2-3).Unlabelled Image
       
  • Iron oxide nanoparticle core-shell magnetic microspheres: Applications
           toward targeted drug delivery
    • Abstract: Publication date: Available online 10 December 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Srinivasan Ayyanaar, Mookkandi Palsamy Kesavan, Chandrasekar Balachandran, Swetha Rasala, Perumal Rameshkumar, Shin Aoki, Jegathalaprathaban Rajesh, Thomas J. Webster, Gurusamy RajagopalAbstractThis study describes a sensitive reactive oxygen species (ROS)-responsive lecithin (LEC) incorporated iron oxide nanoparticle (Fe3O4 NP) system with potent anti-inflammatory properties and even more so when the antioxidant drug curcumin (CUR) is encapsulated in the PLGA hybrid magnetic microsphere system (Fe3O4@LEC-CUR-PLGA-MMS). The delivery system is responsive to ROS including an H2O2 environment to release the payload (CUR) drug. Greater cytotoxicity properties were observed in the presence of Fe3O4@LEC-CUR-PLGA-MMS against A549 and HeLa S3 cells with IC50 values after 24 h of 10 and 12 μg/mL and 10 and 20 μg/mL, respectively. The present Fe3O4@LEC-CUR-PLGA-MMS system demonstrated much better in vitro cytotoxicity, cellular morphological changes and moreover an ability to limit colony formation for A549 and HeLa S3 cancer cell lines than non-cancerous cells, and thus, should be further studied for a wide range of medical applications.Graphical AbstractThe present Fe3O4@LEC-CUR-PLGA-MMS system demonstrated much better in vitro cytotoxicity, cellular morphological changes and moreover ability to control colony formation for A549 and HeLa S3 cancer cell lines than non-cancerous cells, and thus, should be further studied for a wide range of medical applications.Unlabelled Image
       
  • Coating of PLA-nanoparticles with cyclic, arginine-rich cell penetrating
           peptides enables oral delivery of liraglutide
    • Abstract: Publication date: Available online 27 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): P. Uhl, C. Grundmann, M. Sauter, P. Storck, A. Tursch, S. Özbek, K. Leotta, R. Roth, D. Witzigmann, J.A. Kulkarni, V. Fidelj, C. Kleist, P.R. Cullis, G. Fricker, W. MierAbstractUntil today, the oral delivery of peptide drugs is hampered due to their instability in the gastrointestinal tract and low mucosal penetration. To overcome these hurdles, PLA (polylactide acid)-nanoparticles were coated with a cyclic, polyarginine-rich, cell penetrating peptide (cyclic R9-CPP). These surface-modified nanoparticles showed a size and polydispersity index comparable to standard PLA-nanoparticles. The zeta potential showed a significant increase indicating successful CPP-coupling to the surface of the nanoparticles. Cryo-EM micrographs confirmed the appropriate size and morphology of the modified nanoparticles. A high encapsulation efficiency of liraglutide could be achieved. In vitro tests using Caco-2 cells showed high viability indicating the tolerability of this novel formulation. A strongly enhanced mucosal binding and penetration was demonstrated by a Caco-2 binding and uptake assay. In Wistar rats, the novel nanoparticles showed a substantial, 4.5-fold increase in the oral bioavailability of liraglutide revealing great potential for the oral delivery of peptide drugs.Graphical AbstractPLA-nanoparticles were modified with a cyclic cell penetrating peptide. These novel nanoparticles showed a high encapsulation efficiency of liraglutide. Furthermore, the nanoparticles showed no relevant cytotoxicity. In a rodent in vivo study, these particles led to a 4.5-fold increase of the oral uptake of liraglutide.Unlabelled Image
       
  • MXD3 antisense oligonucleotide with superparamagnetic iron oxide
           nanoparticles: A new targeted approach for neuroblastoma
    • Abstract: Publication date: Available online 26 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): MD. Sakiko Yoshida, Connie Duong, Michael Oestergaard, Michael Fazio, Cathy Chen, Rachael Peralta, Shuling Guo, Punit P Seth, Yueju Li, Laurel Beckett, Nitin Nitin, Noriko SatakeAbstractNeuroblastoma (NB) is the most common extracranial solid tumor in children. The outcomes for aggressive forms of NB remain poor. The aim of this study was to develop a new molecular-targeted therapy for NB using an antisense oligonucleotide (ASO) and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), as a delivery vehicle, targeting the transcription regulator MAX dimerization protein 3 (MXD3). We previously discovered that MXD3 was highly expressed in high-risk NB, acting as an anti-apoptotic factor; therefore, it can be a good therapeutic target. In this study, we developed two ASO-NP complexes using electrostatic conjugation to polyethylenimine-coated SPIO NPs and chemical conjugation to amphiphilic polymers on amine-functionalized SPIO NPs. Both ASO-NP complexes demonstrated MXD3 knockdown, which resulted in apoptosis in NB cells. ASO chemically-conjugated NP complexes have the potential to be used in the clinic as they showed great efficacy with minimum NP-associated cytotoxicity.Graphical AbstractTwo nanocomplexes were successfully developed using antisense oligonucleotides (ASOs) and superparamagnetic iron oxide nanoparticles (SPIO NPs). Both complexes silenced the target MAX dimerization protein 3 (MXD3), resulting in cell apoptosis in neuroblastoma cell lines in vitro. ASOs chemically conjugated with amine-functionalized SPIO NP (SHA NP) have therapeutic potential as they demonstrate great MXD3 knockdown (95.8% knockdown compared to untreated) with fewer ASOs per NP than SEI NP complexes, suggesting stable efficient delivery, with minimum NP-associated cytotoxicity.Unlabelled Image
       
  • Effect of nanocomposite coating and biomolecule functionalization on silk
           fibroin based conducting 3D braided scaffolds for peripheral nerve tissue
           engineering
    • Abstract: Publication date: Available online 25 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Mamatha M. Pillai, G Sathish Kumar, Shadi Houshyar, Rajiv Padhye, Amitava BhattacharyyaAbstractIn this work, the effect of carbon nanofiber (CNF) dispersed poly-ε-caprolactone (PCL) nanocomposite coatings and biomolecules functionalization on silk fibroin based conducting braided nerve conduits were studied for enhancing Neuro 2acellular activities. A unique combination of biomolecules (UCM) and varying concentrationsof CNF (5, 7.5, 10% w/w) were dispersed in 10% (w/v) PCL solution for coating on degummed silkthreads. The coated silk threads were braided to develop the scaffold structure. As the concentration of CNFincreased in the coating, the electrical impedance decreased up to 400 Ω indicating better conductivity. The tensile and dynamic mechanical property analysis showed bettermechanical properties in CNF coated samples. In vitro cytocompatibility analysis proved the non-toxicity of the developed braided conduits. Cell attachment, growth and proliferation were significantly enhanced on the biomolecule functionalized nanocomposite coated silk braided structure, exhibiting their potential for peripheral nerve regeneration and recovery.Graphical AbstractUnlabelled Image
       
  • Double layers of gold nanoparticles immobilized titanium implants improve
           the osseointegration in rabbit models
    • Abstract: Publication date: Available online 21 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Wan-Kyu Ko, Seong Jun Kim, Dong Nyoung Heo, In-Bo Han, Sewha Kim, Il Keun Kwon, Seil SohnAbstractOsseointegration is important in osteopenia and osteoporosis patients due to their low bone densities. Gold nanoparticles (GNPs) are greatly beneficial materials as osteogenic agents. The aim of this study is to investigate osseointegration between bones and double layers of GNP-immobilized titanium (Ti) implants. The physicochemical properties of the Ti surface were evaluated by scanning electron microscopy, by atomic force microscopy, by means of the contact angle using water drops, and by x-ray photoelectron spectroscopy. Osteogenic differentiation of human bone-marrow-derived mesenchymal stem cells was analyzed and showed the higher values in double layers of GNP (GNP2) groups. In addition, we performed an in vivo study using hydroxyapatite (HA) and GNP2 spine pedicle screws in ovariectomized (OVX) and SHAM rabbits. Osseointegration parameters also showed higher values in GNP2 than in HA groups. These findings suggest that implants with double layers of GNPs can be a useful alternative in osteoporotic patients.Graphical AbstractThe successful titanium (Ti) implant anchorage depends on strong osseointegration between bones and Ti implants. Specifically, osseointegration is important in osteopenia and osteoporosis patients due to their low bone densities. Gold nanoparticles (GNPs) are highly beneficial materials as osteogenic agents. In this study, we aimed to evaluate the osseointegration between bones and double layers of GNP-immobilized Ti implants. The double layers of GNP-immobilized Ti implants significantly improved the osseointegration than hydroxyapatite coated implants in ovariectomized (OVX) and SHAM rabbit models. These findings suggest that implants with double layers of GNPs can be a useful alternative in osteoporotic patients.Unlabelled Image
       
  • Thiol-antioxidants interfere with assessing silver nanoparticle
           cytotoxicity
    • Abstract: Publication date: Available online 21 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Luiz A.B. Ferreira, Samara Bonesso dos Reis, Emanueli do Nascimento da Silva, Solange Cadore, Juliana da Silva Bernardes, Nelson Durán, Marcelo B. de JesusAbstractMany studies have shown that silver nanoparticles (AgNP) induce oxidative stress, and it is commonly assumed that this is the main mechanism of AgNP cytotoxicity. Most of these studies rely on antioxidants to establish this cause-and-effect relationship; nevertheless, details on how these antioxidants interact with the AgNP are often overlooked. This work aimed to investigate the molecular mechanisms underlying the use of antioxidants with AgNP nanoparticles. Thus, we studied the molecular interaction between the thiol-antioxidants (N-acetyl-L-Cysteine, L-Cysteine, and glutathione) or non-thiol-antioxidants (Trolox) with chemically and biologically synthesized AgNP. Both antioxidants could mitigate ROS production in Huh-7 hepatocarcinoma cells, but only thiol-antioxidants could prevent the cytotoxic effect, directly binding to the AgNP leading to aggregation. Our findings show that data interpretation might not be straightforward when using thiol-antioxidants to study the interactions between metallic nanoparticles and cells. This artifact exemplifies potential pitfalls that could hinder the progress of nanotechnology and the understanding of the nanotoxicity mechanism.Graphical AbstractUnlabelled Image
       
  • Eradication of Cancer stem cells in triple negative breast Cancer using
           Doxorubicin/Pluronic polymeric micelles
    • Abstract: Publication date: Available online 20 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Yi Zhao, Daria Y. Alakhova, Xiangshan Zhao, Vimla Band, Elena V. Batrakova, Alexander V. KabanovAbstractThe potency of polymeric micelle-based doxorubicin, SP1049C, against cancer stem cells (CSCs) in triple negative breast cancer (TNBC) is evaluated. CSCs with high epithelial specific antigen (ESA), high CD44 and low CD24 expression levels were derived from the TNBC cancer cells, MDA-MB-231 and MDA-MB-468. These CSCs were resistant to free doxorubicin (Dox) and displayed increased colony formation, migration, and invasion in vitro, along with higher tumorigenicity in vivo, compared to the parental and non-CSCs counterparts. SP1049C downregulated the expression and inhibited the functional activity of the breast cancer resistance protein (BCRP/ABCG2) in CSCs. The polymeric micelle drug had higher cytotoxicity and potency in reducing the colony formation of CSCs compared to the free drug. It was also more potent in inhibiting the tumor growth in the orthotopic animal tumor models derived from CSCs. These results indicate that SP1049C is active against CSCs and has potential in treating TNBC.Graphical AbstractPluronic-based formulation of doxorubicin, SP1049C (Dox/SP), suppress growth of orthotopic triple negative breast cancer (TNBC) tumors derived from drug resistant cancer stem cells (CSCs) with high epithelial specific antigen (ESA), high CD44 and low CD24 expression levels (A, B) and deplete these CSCs (C) in the tumors. (Graphical Abstract: Figure 6).Unlabelled Image
       
  • PLGA nanocapsules improve the delivery of clarithromycin to kill
           intracellular Staphylococcus aureus and Mycobacterium abscessus
    • Abstract: Publication date: Available online 18 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Frantiescoli Anversa Dimer, Cristiane de Souza Carvalho-Wodarz, Adriely Goes, Katarina Cirnski, Jennifer Herrmann, Viktoria Schmitt, Linda Pätzold, Nadia Abed, Chiara De Rossi, Markus Bischoff, Patrick Couvreur, Rolf Müller, Claus-Michael LehrAbstractDrug delivery systems are promising for targeting antibiotics directly to infected tissues. To reach intracellular Staphylococcus aureus and Mycobacterium abscessus, we encapsulated clarithromycin in PLGA nanocapsules, suitable for aerosol delivery by nebulization of an aqueous dispersion. Compared to the same dose of free clarithromycin, nanoencapsulation reduced 1000 times the number of intracellular S. aureus in vitro. In RAW cells, while untreated S. aureus was located in acidic compartments, the treated ones were mostly situated in non-acidic compartments. Clarithromycin-nanocapsules were also effective against M. abscessus (70–80% killing efficacy). The activity of clarithromycin-nanocapsules against S. aureus was also confirmed in vivo, using a murine wound model as well as in zebrafish. The permeability of clarithromycin-nanocapsules across Calu-3 monolayers increased in comparison to the free drug, suggesting an improved delivery to sub-epithelial tissues. Thus, clarithromycin-nanocapsules are a promising strategy to target intracellular S. aureus and M. abscessus.Graphical AbstractClarithromycin delivery to intracellular bacteria in macrophagesI - Macrophage internalize CS-CLARI-NC that end-ups in lysosomes.II - CLARI can be released in the macrophage cytoplasm and might reach the bacteria inside the vacuole.IIIa - Lysosomes containing CS-CLARI-NC can get closer to the bacteria vacuole.IIIb - CS-CLARI-NC and bacteria compartments are closely associate and CLARI might be released inside the bacteria vacuole.Unlabelled Image
       
  • Doxorubicin loaded pH responsive biodegradable ABA-type Amphiphilic
           PEG-b-aliphatic Polyketal-b-PEG block copolymer for therapy against
           aggressive murine lymphoma
    • Abstract: Publication date: Available online 17 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Sumit Kumar Hira, Kheyanath Mitra, Prateek Srivastava, Shikha Singh, Sambhav Vishwakarma, Ranjeet Singh, Biswajit Ray, Partha Pratim MannaAbstractA novel ABA-type polyethylene glycol (PEG)-b-polyketal (PK)-b-PEG block copolymer was synthesized via click reactions between the monoazido-monomethoxy-PEG and dialkyne terminated aliphatic polyketal with no carboxylic/amide linkages. Formation of the novel block copolymer was confirmed by 1H NMR, GPC, TGA and DSC studies. The formed copolymer has shown faster degradation at acidic pH. Self-assembly of this block copolymer (average size 6.2 nm) was assessed by fluorescence study using pyrene as a probe. Doxorubicin loaded block copolymeric micelles (69.9 nm) have shown pH dependent elevated drug release at pH 6.4, indicating its potential as a pH responsive nano-carrier for anticancer therapy. The nano-sized copolymer demonstrated tumoricidal activities against the lymphoma of murine and human origin with significant levels of growth inhibition and apoptosis. Therapy with doxorubicin loaded copolymer reduced the tumor size and augmented the life span of the tumor bearing animals with improved histopathological parameters, compared with the untreated control.Graphical AbstractAn ABA-type polyethylene glycol (PEG)-b-polyketal (PK)-b-PEG block copolymer with guest molecule doxorubicin was fabricated for therapy against Dalton's lymphoma bearing mice. Therapy with the construct markedly augmented the survival of the animals with tumor compared with untreated littermate. In vitro, the construct is efficient in guest release at low pH inside the cancer cells with enhanced uptake and significant apoptosis.Unlabelled Image
       
  • Enhanced antibacterial performance of ultrathin silver/platinum
           nanopatches by a sacrificial anode mechanism
    • Abstract: Publication date: Available online 15 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Adham Abuayyash, Nadine Ziegler, Hajo Meyer, Michael Meischein, Christina Sengstock, Julian Moellenhoff, Christian Rurainsky, Marc Heggen, Alba Garzón-Manjón, Christina Scheu, Kristina Tschulik, Alfred Ludwig, Manfred KöllerAbstractThe development of antibacterial implant surfaces is a challenging task in biomaterial research. We fabricated a highly antibacterial bimetallic platinum (Pt)/silver(Ag) nanopatch surface by short time sputtering of Pt and Ag on titanium. The sputter process led to a patch-like distribution with crystalline areas in the nanometer-size range (1.3–3.9 nm thickness, 3–60 nm extension). Structural analyses of Pt/Ag samples showed Ag- and Pt-rich areas containing nanoparticle-like Pt deposits of 1–2 nm. The adhesion and proliferation properties of S.aureus on the nanopatch samples were analyzed. Consecutively sputtered Ag/Pt nanopatches (Pt followed by Ag) induced enhanced antimicrobial activity compared to co-sputtered Pt/Ag samples or pure Ag patches of similar Ag amounts. The underlying sacrificial anode mechanism was proved by linear sweep voltammetry. The advantages of this nanopatch coating are the enhanced antimicrobial activity despite a reduced total amount of Ag/Pt and a self-limited effect due the rapid Ag dissolution.Graphical AbstractPlatinum(Pt)/Silver(Ag) nanopatches (1.3–3.9 nm thick, 3–60 nm large) were magnetron-sputtered on a titanium (Ti) substrate using both consecutive sputtering and co-sputtering to generate an antimicrobial surface. Consecutively sputtered Ag/Pt nanopatches induced enhanced antimicrobial activity compared to co-sputtered Pt/Ag samples or pure Ag patches of similar Ag amounts due to a sacrificial anode mechanism accompanied by rapid Ag dissolution.Unlabelled Image
       
  • Desirable PEGylation for improving tumor selectivity of hyaluronic
           acid-based nanoparticles via low hepatic captured, long circulation times
           and CD44 receptor-mediated tumor targeting
    • Abstract: Publication date: Available online 15 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Chao Teng, Zhuodong Chai, Zhongyue Yuan, Lianjie Ren, Chenshi Lin, Zhen Yan, Wei He, Chao Qin, Lei Yang, Xiaopeng Han, Lifang YinAbstractPEG coating was regarded as one effective method to improve the tumor-targeting efficiency of hyaluronic acid-based nanoparticles (HBN). However, the research of interaction between PEG coating and different receptors such as stabilin-2 and CD44 was limited. Herein, we synthesized a series of PEGylated hyaluronic acid with Curcumin (PHCs) to evaluate the role of PEG coating density in the interaction between HA and its receptors, which influenced tissues targeting, pharmacokinetic profiles and therapeutic efficacy of HBN. Compared with other counterparts, PHC HBN with about 5% PEG coating density preferably accumulated in the tumor mass, rather than in the liver, hold desirable anti-cancer effect. These results indicated to obtain optimized the anticancer effect of HBN, the cellular uptake efficiency between different types of the cells was carefully balanced by different PEG densities.Graphical AbstractIllustration of pegylated hyaluronic acid (HA) based nanoparticles that effectively targets and suppresses breast cancer by balancing the cellular uptake efficiency among different type cells via peg coating density.Unlabelled Image
       
  • Core-shell insulin-loaded nanofibrous scaffolds for repairing diabetic
           wounds
    • Abstract: Publication date: Available online 8 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Chen-Hung Lee, Kuo-Chun Hung, Ming-Jer Hsieh, Shang-Hung Chang, Jyuhn-Huarng Juang, I-Chang Hsieh, Ming-Shien Wen, Shih-Jung LiuAbstractPatients with diabetes mellitus have up to a 15% lifetime risk of non-healing and poorly healing wounds. This work develops core-shell nanofibrous bioactive insulin-loaded poly-D-L-lactide-glycolide (PLGA) scaffolds that release insulin in a sustained manner for repairing wounds in diabetic rats. To prepare the biodegradable core-shell nanofibers, PLGA and insulin solutions were fed into two capillary tubes of different sizes that were coaxially electrospun using two independent pumps. The scaffolds sustainably released insulin for four weeks. The hydrophilicity and water-containing capacity of core-shell nanofibrous insulin/PLGA scaffolds significantly exceeded those of blended nanofibrous scaffolds. The nanofibrous core-shell insulin-loaded scaffold reduced the amount of type I collagen in vitro, increased the transforming growth factor-beta content in vivo, and promoted diabetic would repair. The core-shell insulin-loaded nanofibrous scaffolds prolong the release of insulin and promote diabetic wound healing.Graphical AbstractAccelerate the healing wound following treatment using functionally active insulin released from insulin-loaded nanofibrous scaffolds.Unlabelled Image
       
  • PEG-DAAO conjugate: A promising tool for cancer therapy optimized by
           protein engineering
    • Abstract: Publication date: Available online 6 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Elena RosiniAbstractThe flavoenzyme D-amino acid oxidase (DAAO) represents a potentially good option for enzyme prodrug therapy as it produces H2O2 using D-amino acids as substrates, compounds present at low concentration in vivo and that can be safely administered to regulate H2O2 production. We optimized the cytotoxicity of the treatment by: i) using an efficient enzyme variant active at low O2 and D-alanine concentrations (mDAAO); ii) improving the stability and half-life of mDAAO and the enhanced permeability and retention effect by pegylation; and iii) inhibiting the antioxidant cellular system by a heme oxygenase-1 inhibitor (ZnPP). A very low amount of PEG-mDAAO (10 mU, 50 ng of enzyme) induces cytotoxicity on various tumor cell lines. Notably, PEG-mDAAO seems well suited for in vivo evaluation as it shows the same cytotoxicity at air saturation (21%) and 2.5% O2, a condition resembling the microenvironment found in the central part of tumors.Graphical AbstractOptimization of an enzyme prodrug therapy approach based on H2O2 production. The recombinant, engineered PEG-mDAAO conjugate induces a selective cytotoxicity on different tumor cell lines especially when the ZnPP HO-1 inhibitor is simultaneously administered. This system allows to generate ROS species also at low oxygen concentration, as occurs during tumor growth.Unlabelled Image
       
  • Sustained release of arsenic trioxide benefits interventional therapy on
           rabbit VX2 liver tumor
    • Abstract: Publication date: Available online 31 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Xin Fu, Rong-guang Luo, Wei Qiu, Lu Ouyang, Guang-qin Fan, Qing-rong Liang, Qun TangAbstractThe benefit of chemotherapy as a constituent of transcatheter arterial chemoembolization (TACE) is still in debate. Recently we have developed arsenic trioxide nanoparticle prodrug (ATONP) as a new anticancer drug, but its systemic toxicity is a big issue. In this preclinical TACE study, ATONP emulsified in lipiodol behaved as drug - eluting bead manner. Sustained release of arsenic from ATONP within occluded tumor caused very low arsenic level in plasma, avoiding the “rushing out” effect as ATO did. Correspondingly, intratumoral arsenic accumulation and inorganic phosphate deprivation were simultaneously observed, and arsenic concentration was much higher as ATONP was transarterially administered than ATO, or intravenously injected. Tumor necrosis and apoptosis were remarkably more severe in ATONP group than ATO, but no significant hepatic and renal toxicity was perceived. In brief, ATONP alleviated arsenic toxicity and boosted the therapeutic effect of TACE via Pi-activated drug sustainable release.Graphical AbstractIn the preclinical transcatheter arterial chemoembolization study, arsenic trioxide nanoparticle prodrug emulsified in lipiodol behaved as drug-eluting bead. Anticancer arsenic trioxide was sustainably released from the prodrug via deprivation of intratumoral inorganic phosphate, and thereby enhanced interventional therapy by inducing severe necrosis and apoptosis of VX2 tumor. Arsenic and gadolinium toxicity was minimized due to sustained release and favorable elimination. Therefore, the prodrug might have potential to benefit clinical TACE therapy. Additionally, nanomedicine being plagued with low delivery efficacy comes in a dilemma and our results indicate that interventional radiology might help address this tough problem.Unlabelled Image
       
  • Selective nano-thermal therapy of human retinoblastoma in retinal laser
           surgery
    • Abstract: Publication date: Available online 31 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Ramin Khademi, Abolhassan RazminiaAbstractIn this research, an experimental validated predictive finite element model of a cancerous human eye is developed to investigate how the tumor cells in retinoblastoma can be selectively damaged in the course of laser irradiation. In the computational modeling, the tumor is assumed to be in the initial growth stages and located in the macular zone. The statistical calculations testify that an 8.5% improvement in our estimation of the experimental temperature inside the normal human eye compared to those provided by the previous model has been achieved. Under the surgical conditions, the at-risk regions are determined, and the thermal responses of the tissue to various intrinsic and operating factors are obtained and discussed. Our findings indicate that, in the same amount of exposure time, introducing biodegradable nanoparticles in a concentration of 0.2 into the tumor tissue can increase the lethal zone area by 51 percent, and could plays an effective role in surviving of corneal injury.Graphical AbstractAn experimental verified theoretical model has been developed that can explain how the cells in retinoblastoma are selectively damaged in the course of nano-photothermal therapy. After having discussed the clinical aspects and effectiveness of the treatment, some new ideas for developing this approach to investigate ambiguous sides of the issue and for protecting cornea from the hazard of optical side-effects of the laser treatment are proposed.Unlabelled Image
       
  • A versatile theranostic nanodevice based on an orthogonal bioconjugation
           strategy for efficient targeted treatment and monitoring of triple
           negative breast cancer
    • Abstract: Publication date: Available online 30 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): María Victoria Cano-Cortés, Saúl Abenhamar Navarro-Marchal, María Paz Ruiz-Blas, Juan José Díaz-Mochón, Juan Antonio Marchal, Rosario M. Sánchez-MartínAbstractA novel chemical-based orthogonal bioconjugation strategy to produce tri-functionalised nanoparticles (NPs) carrying doxorubicin (DOX), near-infrared cyanine dye (Cy7) and a homing peptide CRGDK, a peptide specifically binds to neuropilin-1 (Nrp-1) overexpressed on triple negative breast cancer (TNBC) cells, has been validated. These theranostic NPs have been evaluated in vitro and in vivo using an orthotopic xenotransplant mouse model using TNBC cells. In vitro assays show that theranostic NPs improve the therapeutic index in comparison with free DOX. Remarkably, in vivo studies showed preferred location of theranostic NPs in the tumor area reducing the volume at the same level than free DOX while presenting lower side effects. This multifunctionalized theranostic nanodevice based on orthogonal conjugation strategies could be a good candidate for the treatment and monitoring of Nrp-1 overexpressing tumors. Moreover, this versatile nanodevice can be easily adapted to treat and monitor different cancer types by adapting the conjugation strategy.Graphical AbstractAn effective, safe and versatile nanodevice for in vivo theranostic to target tumor vasculature has been successfully developed. Herein, we reported a theranostic nanodevice based on orthogonal conjugation strategies for the multifunctionalization of polymeric NPs that contain a controlled amount of each one of the bioactive cargoes. As proof of concept, NPs carrying doxorubicin (DOX), near-infrared cyanine dye (Cy7) and a homing peptide (CRGDK), which can actively recognize a receptor overexpressed in triple negative breast cancer have been successfully validated in vitro using MDA-MB-231 tumor cell line and in vivo using an orthotopic breast cancer xenotransplant mouse model.Unlabelled Image
       
  • Vitamin c: One compound, several uses. Advances for delivery, efficiency
           and stability
    • Abstract: Publication date: Available online 30 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Amanda C. Caritá, Bruno Fonseca Santos, Jemima Daniela Shultz, Bozena Michniak-Kohn, Marlus Chorilli, Gislaine Ricci LeonardiAbstractVitamin C (Vit C) is a potent antioxidant with several applications in the cosmetic and pharmaceutical fields. However, the biggest challenge in the utilization of Vit C is to maintain its stability and improve its delivery to the active site. Several strategies have been developed such as: controlling the oxygen levels during formulation and storage, low pH, reduction of water content in the formulation and the addition of preservative agents. Additionally, the utilization of derivatives of Vit C and the development of micro and nanoencapsulated delivery systems have been highlighted. In this article, the multiple applications and mechanisms of action of vitamin C will be reviewed and discussed, as well as the new possibilities of delivery and improvement of stability.Graphical AbstractVitamin C (Vit C) is a potent antioxidant with several applications in the cosmetic and pharmaceutical fields. However, the biggest challenge in the utilization of Vit C is to maintain its stability and improve its delivery to the active site. In this article, the multiple applications and mechanisms of action of vitamin C will be reviewed and discussed, as well as the new possibilities of delivery and improvement of stability.Unlabelled Image
       
  • Acid-activatable polymeric curcumin nanoparticles as therapeutic agents
           for osteoarthritis
    • Abstract: Publication date: Available online 28 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Changsun Kang, Eunkyeong Jung, Hyejin Hyeon, Semee Seon, Dongwon LeeAbstractCurcumin, a primary active element of turmeric, has potent antioxidant and anti-inflammatory activity, but its low bioavailability is a major hurdle in its pharmaceutical applications. To enhance the therapeutic efficacy of curcumin, we exploited polymeric prodrug strategy. Here, we report rationally designed acid-activatable curcumin polymer (ACP), as a therapeutic prodrug of curcumin, in which curcumin was covalently incorporated in the backbone of amphiphilic polymer. ACP could self-assemble to form micelles that rapidly release curcumin under the acidic condition. The potential of ACP micelles as therapeutics for osteoarthritis was evaluated using a mouse model of monoidoacetic acid (MIA)-induced knee osteoarthritis. ACP micelles drastically protected the articular structures from arthritis through the suppression of tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). Given their pathological stimulus-responsiveness and potent antioxidant and anti-inflammatory activities, ACP micelles hold remarkable potential as a therapeutic agent for not only osteoarthritis but also various inflammatory diseases.Graphical AbstractAcid-responsive anti-inflammatory curcumin polymer, termed ACP is rationally designed to incorporate curcumin in the backbone of acid-sensitive amphiphilic poly(β-amino ester). ACP could form micelles through self-assembly that rapidly release curcumin and recover fluorescence signal in the acidic inflammatory site. ACP micelles enhance fluorescence signals and drastically protect the articular structures from arthritis through the suppression of tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). Given their pathological stimulus-responsiveness and potent antioxidant and anti-inflammatory activities, ACP micelles hold remarkable potential in the capacity of a therapeutic agent for osteoarthritis.Unlabelled Image
       
  • The Promotion of Bone Regeneration through CS/GP-CTH/antagomir-133a/b
           Sustained Release System
    • Abstract: Publication date: Available online 28 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Fusong Jiang, Fuli Yin, Yiwei Lin, Wenyang Xia, Lihui Zhou, Chenhao Pan, Nan Wang, Haojie Shan, Zubin Zhou, Xiaowei YuAbstractFew studies reported the application of miRNA in bone regeneration. In this study, the expression of miR133a and miR133b in murine BMSCs was inhibited via antagomiR-133a/b and the osteogenic differentiation in murine BMSCs was evaluated. The RT-PCR, flow cytometry, cell counting kit-8, and annexin V-FITC/PI double staining assays were performed. Double knockdown miR133a and miR133b can promote BMSC osteogenic differentiation. At optimum N/P ration (15:1), the loading efficiency can reach over 90%. CTH-antagomiR-133a/b showed no cytotoxicity to BMSCs and diminished miR133a and miR133b expression in BMSCs. Furthermore, chitosan-based sustained delivery system can continuous dose CTH-antagomiR-133a/b and calcium deposition and osteogenic specific gene expression were enhanced in vitro. The new bone formation was enhanced after the sustained delivery system containing CTH-antagomiR-133a/b nanoparticles was used in mouse calvarial bone defect model. Our results demonstrate that CTH nanoparticles could facilitate continuous dosing of antagomiR133a/b, which can promote osteogenic differentiation.Graphical AbstractThe new bone formation was enhanced after the sustained delivery system containing CTH-antagomiR-133a/b nanoparticles was used in mouse calvarial bone defect model. Above results demonstrated that continuous dosing of antagomiR133a/b can promote osteogenic differentiation and CTH nanoparticles could be considered as a potential candidate as an efficient non-viral miRNA carrier for the miRNA-based therapy.Unlabelled Image
       
  • Encapsulation in lipid-core nanocapsules improves topical treatment with
           the potent antileishmanial compound CH8
    • Abstract: Publication date: Available online 28 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Douglas O Escrivani, Milene Valéria Lopes, Fernanda Poletto, Stela Regina Ferrarini, Ariane J. Sousa-Batista, Patrick G. Steel, Sílvia Stanisçuaski Guterres, Adriana Raffin Pohlmann, Bartira Rossi-BergmannAbstractCutaneous leishmaniasis (CL) is a neglected parasitic disease conventionally treated by multiple injections with systemically toxic drugs. Aiming at a more acceptable therapy, we developed lipid-core nanocapsules (LNC) entrapping the potent antileishmanial chalcone (CH8) for topical application. Rhodamine-labeled LNC (Rho-LNC-CH8) was produced for imaging studies. LNC-CH8 and Rho-LNC-CH8 had narrow size distributions (polydispersity index
       
  • Zileuton™ loaded in polymer micelles effectively reduce breast Cancer
           circulating tumor cells and intratumoral Cancer stem cells
    • Abstract: Publication date: Available online 27 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Petra Gener, Sara Montero, Helena Xandri-Monje, Zamira V. Díaz-Riascos, Diana Rafael, Fernanda Andrade, Francesc Martínez-Trucharte, Patricia González, Joaquin Seras-Franzoso, Albert Manzano, Diego Arango, Joan Sayós, Ibane Abasolo, Simo SchwartzAbstractTumor recurrence, metastatic spread and progressive gain of chemo-resistance of advanced cancers are sustained by the presence of cancer stem cells (CSCs) within the tumor. Targeted therapies with the aim to eradicate these cells are thus highly regarded. However, often the use of new anti-cancer therapies is hampered by pharmacokinetic demands. Drug delivery through nanoparticles has great potential to increase efficacy and reduce toxicity and adverse effects. However, its production has to be based on intelligent design. Likewise, we developed polymeric nanoparticles loaded with Zileuton™, a potent inhibitor of cancer stem cells (CSCs), which was chosen based on high throughput screening. Its great potential for CSCs treatment was subsequently demonstrated in in vitro and in in vivo CSC fluorescent models. Encapsulated Zileuton™ reduce amount of CSCs within the tumor and effectively block the circulating tumor cells (CTCs) in the blood stream and metastatic spread.Graphical AbstractDrug delivery has great potential to increase the systemic efficacy and, reduce toxicity and adverse effects of drugs. We developed and synthesized polymeric micelles loaded with Zileuton™, a potent inhibitor of ALOX5 in Cancer Stem Cells (CSCs), which was chosen as a therapeutic target candidate based on high throughput screening data. Its great potential for CSCs treatment was subsequently demonstrated in vitro and in vivo in breast CSCs fluorescent models. PM-Zileuton™ show strong reduction of the amount of intratumoral CSCs and further, of blood circulating CSCs in vivo.Unlabelled Image
       
  • Enriched chitosan nanoparticles loaded with siRNA are effective in
           lowering Huntington's disease gene expression following intranasal
           administration
    • Abstract: Publication date: Available online 27 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Vasyl Sava, Oksana Fihurka, Anastasia Khvorova, Juan Sanchez-RamosAbstractTherapies to lower gene expression in brain disease currently require chronic administration into the cerebrospinal fluid (CSF) by intrathecal infusions or direct intracerebral injections. Though well-tolerated in the short-term, this approach is not tenable for a life-time of administration. Nose-to-brain delivery of enriched chitosan-based nanoparticles loaded with anti-HTT siRNA was studied in a transgenic YAC128 mouse model of Huntington's Disease (HD). A series of chitosan-based nanoparticle (NP) formulations encapsulating anti-HTT small interfering RNA (siRNA) were designed to protect the payload from degradation “en route” to the target. Factors to improve production of effective nanocarriers of anti-HTT siRNA were identified and tested in a YAC128 mouse model of Huntington's disease. Four formulations of nanocarriers were identified to be effective in lowering HTT mRNA expression by at least 50%. Intranasal administration of nanoparticles carrying siRNA is a promising therapeutic alternative for safe and effective lowering of mutant HTT expression.Graphical AbstractA)Nanoparticles (NP) were synthesized by polyelectrolyte complexation of chitosan (CS) with anti-HTT siRNA and matrices were cross-linked with Mangafodipir. Flow chart of NP fabrication. P = provisional preparation; E = enriched preparation. Enrichment factor (EF) was calculated by formula: EF = Vp/Ve, where Vp volume of provisional preparation and Ve = volume of enriched preparation.B)A series of NP formulations loaded with anti-HTT siRNA were tested in a Tg mouse model of Huntington's Disease (Tg YAC128). Intranasal administration of NPs was followed by euthanasia and brain dissection at 48 and 120 hrs.C)Sampling by micro-punch of olfactory bulb (OB), cerebral cortex (CTX), corpus striatum (ST) and hippocampus (HI)D)Assays of HTT mRNA and protein in brain tissue samples revealed significant lowering of HTT expression in all four regions of brain.Unlabelled Image
       
  • Drug-loaded titanium dioxide nanoparticle coated with tumor targeting
           polymer as a sonodynamic chemotherapeutic agent for anti-cancer therapy
    • Abstract: Publication date: Available online 27 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Seonil Kim, Sooseok Im, Eun-yeong Park, Junseok Lee, Chulhong Kim, Tae-il Kim, Won Jong KimAbstractSonodynamic therapy utilizes ultrasound (US)-responsive generation of reactive oxygen species (ROS) from sonosensitizer, and it is a powerful strategy for anti-cancer treatment in combination with chemotherapy. Herein, we report a precisely designed sonodynamic chemotherapeutics which exhibits US-responsive drug release via ROS generation from co-loaded sono-sensitizer. Doxorubicin (DOX)-coordinated titanium dioxide nanoparticles (TNP) were encapsulated with polymeric phenyboronic acid (pPBA) via phenylboronic ester bond between pPBA and DOX. Loaded DOX was readily released under US irradiation due to the ROS-cleavable characteristics of phenylboronic ester bond. The size of nanoparticles was around 200 nm, and DOX was released by ROS generated under US irradiation. Tumor targeting by PBA moiety, intracellular ROS generation, and combined therapeutic effect against tumor cells were confirmed in vitro. Finally, we demonstrated high tumor accumulation and efficient tumor growth inhibition in tumor-bearing mice under US irradiation, which revealed potential as a multi-functional agent for sonodynamic chemotherapy.Graphical AbstractDOX-coordinated TNP was coated with pPBA via formation of boronic ester bond, leading to pPBA@TNP-DOX nanoparticle, which has high tumor targeting ability by the specific interaction between PBA and sialylated epitope of cancer cells. When irradiated by ultrasound, DOX could be released from pPBA@TNP-DOX via cleavage of boronic ester bonding induced by ultrasound-mediated ROS generation. Tumor cell death could be obtained by ROS as well as DOX-mediated cell death, indicating that pPBA@TNP-DOX has a potential as an agent for sonodynamic and chemotherapy.Unlabelled Image
       
  • Co-delivery of Poria cocos extract and doxorubicin as an ‘all-in-one’
           nanocarrier to combat breast cancer multidrug resistance during
           chemotherapy
    • Abstract: Publication date: Available online 25 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Yanan Li, Xiaolian Li, Yang Lu, Birendra Chaurasiya, Gujie Mi, Di Shi, Daquan Chen, Thomas J. Webster, Jiasheng Tu, Yan ShenAbstractRecent studies have indicated that multidrug resistance (MDR) can significantly limit the effects of conventional chemotherapy. In this study, PT (Pachymic acid and dehydrotumulosic acid) are the two major triterpenoid components purified and identified in P. cocos. A liposomal co-delivery system encapsulating doxorubicin (DOX) and PT was prepared. Notably, the mechanism of PT reversed P-glycoprotein (P-gp) mediated MDR mainly relied on the inhibition of the P-gp function, which further decreased the levels of P-gp and caveolin-1 proteins. In drug-resistant MCF cells, co-administration with 5 μg/ml PT significantly enhanced sensitivity of DOX. Finally, liposome-mediated co-delivery with PT significantly improved the anti-tumor effect of DOX in tumor-bearing mice when compared to other single therapy groups. In conclusion, this study showed for the first time that DOX and PT act synergistically as an “all-in-one” treatment to reverse MDR during tumor treatment and, thus, should be studied further for a wide range of anti-cancer applications.Graphical AbstractUnlabelled Image
       
  • Biodistribution of TAT or QLPVM coupled to receptor targeted liposomes for
           delivery of anticancer therapeutics to brain in vitro and in vivo
    • Abstract: Publication date: Available online 25 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Sushant Lakkadwala, Bruna dos Santos Rodrigues, Chengwen Sun, Jagdish SinghAbstractCombination therapy has emerged as an efficient way to deliver chemotherapeutics for treatment of glioblastoma. It provides collaborative approach of targeting cancer cells by acting via multiple mechanisms, thereby reducing drug resistance. However, the presence of impermeable blood brain barrier (BBB) restricts the delivery of chemotherapeutic drugs into the brain. To overcome this limitation, we designed a dual functionalized liposomes by modifying their surface with transferrin (Tf) and a cell penetrating peptide (CPP) for receptor and adsorptive mediated transcytosis, respectively. In this study, we used two different CPPs (based on physicochemical properties) and investigated the influence of insertion of CPP to Tf-liposomes on biocompatibility, cellular uptake, and transport across the BBB both in vitro and in vivo. The biodistribution profile of Tf-CPP liposomes showed more than 10 and 2.7 fold increase in doxorubicin and erlotinib accumulation in mice brain, respectively as compared to free drugs with no signs of toxicity.Graphical AbstractBlood brain barrier prevents the delivery of chemotherapeutics into brain. To overcome this issue, we designed a doxorubicin and erlotinib loaded dual functionalized liposomal delivery system, surface modified with transferrin (Tf) and a cell penetrating peptide to enhance their translocation across the BBB into glioblastoma tumor in brain via receptor mediated transcytosis and enhanced cell penetration, both in vitro and in vivo. Our results demonstrated several fold increase in the concentration of anticancer drugs across the co-culture endothelial barrier as well as in mice brain. Thus, we believe that this study would have high impact for treating patients with glioblastoma.Unlabelled Image
       
  • PEGylated mucus-penetrating nanocrystals for lung delivery of a new FtsZ
           inhibitor against Burkholderia cenocepacia infection
    • Abstract: Publication date: Available online 25 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Gabriella Costabile, Romina Provenzano, Alberto Azzalin, Viola Camilla Scoffone, Laurent R. Chiarelli, Valeria Rondelli, Isabelle Grillo, Thomas Zinn, Alexander Lepioshkin, Svetlana Savina, Agnese Miro, Fabiana Quaglia, Vadim Makarov, Tom Coenye, Paola Brocca, Giovanna Riccardi, Silvia Buroni, Francesca UngaroAbstractC109 is a potent but poorly soluble FtsZ inhibitor displaying promising activity against Burkholderia cenocepacia, a high-risk pathogen for cystic fibrosis (CF) sufferers. To harness C109 for inhalation, we developed nanocrystal-embedded dry powders for inhalation suspension consisting in C109 nanocrystals stabilized with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) embedded in hydroxypropyl-β-cyclodextrin (CD). The powders could be safely re-dispersed in water for in vitro aerosolization. Owing to the presence of a PEG shell, the rod shape and the peculiar aspect ratio, C109 nanocrystals were able to diffuse through artificial CF mucus. The promising technological features were completed by encouraging in vitro/in vivo effects. The formulations displayed no toxicity towards human bronchial epithelial cells and were active against planktonic and sessile B. cenocepacia strains. The efficacy of C109 nanosuspensions in combination with piperacillin was confirmed in a Galleria mellonella infection model, strengthening their potential for combined therapy of B. cenocepacia lung infections.Graphical AbstractDry powders for inhalation suspension embedding TPGS-stabilized nanocrystals of the new anti-burkholderia agent C109 were successfully developed. The PEG shell and the peculiar aspect ratio of the nanocrystals concurred to drug diffusion through artificial mucus. The developed C109 nanocrystal-embedded dry powders: i) maintain a broad-spectrum antimicrobial activity; ii) improve the inhibition ability of C109 against B. cenocepacia biofilm; ii) are safe at microbiologically active concentrations towards human bronchial epithelial cells; iii) exert in vivo a synergistic activity with piperacillin, a conventional antibiotic for treatment of B. cenocepacia lung infections.Unlabelled Image
       
  • A cationic Amphiphilic co-polymer as a carrier of nucleic acid
           nanoparticles (Nanps) for controlled gene silencing, Immunostimulation,
           and biodistribution
    • Abstract: Publication date: Available online 25 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Justin R. Halman, Ki-Taek Kim, So-Jung Gwak, Richard Pace, Morgan Brittany Johnson, Morgan R. Chandler, Lauren Rackley, Mathias Viard, Ian Marriott, Jeoung Soo Lee, Kirill A. AfoninAbstractProgrammable nucleic acid nanoparticles (NANPs) provide controlled coordination of therapeutic nucleic acids (TNAs) and other biological functionalities. Beyond multivalence, recent reports demonstrate that NANP technology can also elicit a specific immune response, adding another layer of customizability to this innovative approach. While the delivery of nucleic acids remains a challenge, new carriers are introduced and tested continuously. Polymeric platforms have proven to be efficient in shielding nucleic acid cargos from nuclease degradation while promoting their delivery and intracellular release. Here, we venture beyond the delivery of conventional TNAs and combine the stable cationic poly-(lactide-co-glycolide)-graft-polyethylenimine with functionalized NANPs. Furthermore, we compare several representative NANPs to assess how their overall structures influence their delivery with the same carrier. An extensive study of various formulations both in vitro and in vivo reveals differences in their immunostimulatory activity, gene silencing efficiency, and biodistribution, with fibrous NANPs advancing for TNA delivery.Graphical AbstractFunctional nucleic acid nanoparticles (NANPs) are combined with the novel polymeric carrier for potent gene silencing and controllable immunostimulation. Optimization of the formulation is achieved and efficacy is demonstrated against several targets. Biodistribution, hemocompatibility, and immunotoxicity are assessed to identify how NANP structure determines therapeutic outcomes.Unlabelled Image
       
  • Phosphatidylserine (Ps) and Phosphatidylglycerol (Pg) Nanodispersions as
           potential anti-inflammatory therapeutics: Comparison of In Vitro activity
           and impact of Pegylation
    • Abstract: Publication date: Available online 25 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Miriam Elisabeth Klein, Simone Mauch, Max Rieckmann, Dailén Garcia Martinez, Gerd Hause, Michel Noutsias, Ulrich Hofmann, Henrike Lucas, Annette Meister, Gustavo Ramos, Harald Loppnow, Karsten MäderAbstractPhosphatidylserine (PS) and phosphatidylglycerol (PG) are endogenous phospholipids with putative anti-inflammatory potential. However, studies comparing PS and PG are rare and were mainly conducted with phospholipid-dispersions of large size and broad distributions. Thus, we prepared small-sized PS- and PG-loaded liposomes exhibiting narrow distribution, and additionally studied the impact of liposome-pegylation on the reduction of the TNFα-production caused by the PS- and PG-liposomes. These PS- and PG-containing nanodispersions had a small size around 100 nm and a narrow distribution (PDI 
       
  • Synchronized Rayleigh and Raman scattering for the characterization of
           single optically trapped extracellular vesicles
    • Abstract: Publication date: Available online 24 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Agustin Enciso-Martinez, Edwin van der Pol, Aufried T.M. Lenferink, Leon W.M.M. Terstappen, Ton G. Van Leeuwen, Cees OttoAbstractExtracellular Vesicles (EVs) can be used as biomarkers in diseases like cancer, as their lineage of origin and molecular composition depend on the presence of cancer cells. Recognition of tumor-derived EVs (tdEVs) from other particles and EVs in body fluids requires characterization of single EVs to exploit their biomarker potential. We present here a new method based on synchronized Rayleigh and Raman light scattering from a single laser beam, which optically traps single EVs. Rapidly measured sequences of the Rayleigh scattering amplitude show precisely when an individual EV is trapped and the synchronously acquired Raman spectrum labels every time interval with chemical information. Raman spectra of many single EVs can thus be acquired with great fidelity in an automated manner by blocking the laser beam at regular time intervals. This new method enables single EV characterization from fluids at the single particle level.Graphical AbstractExtracellular Vesicles (EVs) are involved in numerous diseases, such as cancer and can be used as biomarkers. As the lineage of origin and molecular composition of EVs can vary significantly, characterization of single EVs is required to fully exploit their biomarker potential. We developed a procedure of synchronized Rayleigh and Raman scattering for the characterization of single optically trapped EVs in a fluid. The time trace of the Rayleigh scattering amplitude shows with great precision when an individual EV is trapped and the synchronously measured Raman spectra reveals chemical information. This new method is generally applicable to single particle analysis.Unlabelled Image
       
  • Development of anti-matrix metalloproteinase-2 (MMP-2) nanobodies as
           potential therapeutic and diagnostic tools
    • Abstract: Publication date: Available online 24 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): A. Marturano, M. Hendrickx, E. Falcinelli, M. Sebastiano, G. Guglielmini, G. Hassanzadeh-Ghassabeh, S. Muyldermans, P. Declerck, P. GreseleAbstractMatrix metalloproteinase-2 (MMP-2) is an endopeptidase involved in cardiovascular disease and cancer. To date, no highly selective MMP-2 inhibitors have been identified for potential use in humans.Aim of our work was to apply the nanobody technology to the generation of highly selective inhibitors of human MMP-2 and to assess their effects on platelet function and their applicability as conjugated nanobodies.We constructed a nanobody library after immunising an alpaca with human active MMP-2 and identified, after phage display and screening, one MMP-2 inhibitory nanobody (VHH-29), able to hinder the effects of MMP-2 on platelet activation, and one nanobody not inhibiting MMP-2 activity (VHH-136) which, chemically conjugated to a fluorescent probe, allowed the detection of human MMP-2 by flow-cytometry and immune-cytochemistry.In conclusion, we have generated and characterized two new nanotechnological molecular tools for human MMP-2, which represent promising agents for the study of MMP-2 in cardiovascular pathophysiology.Graphical AbstractAntibodies represent essential research tools and a well-established and expanding class of diagnostics and therapeutics. Our study apply the nanobody technology to the generation of a novel highly selective inhibitor, displaying potentially safe anti athero-thrombotic effects and of an high affinity fluorescent probe specific for human MMP-2, applicable as diagnostic tools for visualisation and quantification of MMP-2 activity.Unlabelled Image
       
  • Nose-to-brain co-delivery of repurposed simvastatin and BDNF
           synergistically attenuates LPS-induced Neuroinflammation
    • Abstract: Publication date: Available online 23 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Dharani Manickavasagam, Li Lin, Moses O. OyewumiAbstractA therapeutic strategy that can combat the multifaceted nature of neuroinflammation pathology was investigated. Thus, we fabricated PEG-PdLLA polymersomes and evaluated the efficacy in co-delivery of simvastatin (Sim, as a repurposed anti-inflammatory agent) with brain derived neurotrophic factor (BDNF, as an exogeneous trophic factor supplementation). Using LPS model of neuroinflammation, intranasal administration of combination drug-loaded polymersomes (containing both Sim and BDNF; Sim-BDNF-Ps) markedly down-regulated brain levels of cytokines compared to free drug and single-drug-loaded polymersomes. Further, Sim-BDNF-Ps effectively replenished brain level of BDNF, that was depleted following neuroinflammation, resulting in a 2-fold BDNF increase versus untreated LPS control group. We found out that the efficiency of the combination drug-loaded polymersomes to suppress microglia activation in brain regions followed the order: frontal cortex ˃ striatum ˃ hippocampus. Our findings indicated that Sim-BDNF-Ps could effectively inhibit microglial-mediated inflammation as well as potentially resolve the neurotoxic microenvironment that is often associated with neuroinflammation.Graphical AbstractThe schematic provides the underlying processes involved in neuroinflammation including continuous activation of immune cells, microglia, that leads to release of neurotoxic factors. Our study examines the therapeutic application of combination drug which include repurposed simvastatin and brain-derived neurotrophic factor (BDNF) formulated into a polymersomes platform. The polymersome formulation was administered via intranasal route in a mouse model of neuroinflammation to bypass the blood–brain barrier. Our proposed approach not only addresses both microglia activation and the damaging effects on neurons but also improves brain distribution and maintains biological activity of neurotherapeutics through polymersome-based delivery systems.Unlabelled Image
       
  • Direct interaction of fibrinogen with lipid microparticles modulates
           clotting kinetics and clot structure
    • Abstract: Publication date: Available online 23 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Dzhigangir Faizullin, Yuliya Valiullina, Vadim Salnikov, Yuriy ZuevAbstractExtensive studies revealed the role of blood lipid microparticles (liposomes, microvesicles) in activation of coagulation cascade. The direct interaction of fibrinogen/fibrin with lipid surfaces and its consequence for hemostasis received much less attention. Pronounced changes both in clot morphology and kinetics of fibrin clotting in the presence of artificial liposomes were observed. The evidence was obtained that lipid microparticles per se present a diffusion barrier to the three-dimensional fibril assembling and pose spatial restrictions for fiber elongation. On the other hand, fibrinogen adsorption results in its high local concentration on liposome surface that accelerates fibrin polymerization. Adsorption induces Fg secondary structure alterations which may contribute to the abnormal clot morphology. In dependence on lipid composition and size of microparticles, the interplay of these mechanisms determines functionally important alterations of clot morphology. The obtained results contribute to the knowledge of clotting mechanisms in the presence of artificial and natural lipid microparticles.Graphical AbstractFibrinogen interacts with lipid microparticles (LMP), circulating in blood. Both the composition and size of LMPs could have impact on clot morphology. Fibrinogen adsorption on LMP surface in the end-on orientation could greatly accelerate fibrin polymerization and favors the incorporation of LMPs into clot structure. Side-on orientation of adsorbed molecules makes them inactive. Besides, LMPs pose a spatial barrier to fibrin elongation, resulting in porous clots of branched fibers. Thus, direct fibrinogen – LMP interactions contribute to hemostasis, which should been taken into account upon analyzing the clotting deceases and engineering of artificial lipid particles.Unlabelled Image
       
  • Nonviral polymeric nanoparticles for gene therapy in pediatric CNS
           malignancies
    • Abstract: Publication date: Available online 23 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): John Choi, Yuan Rui, Jayoung Kim, Noah Gorelick, David R. Wilson, Kristen Kozielski, Antonella Mangraviti, Eric Sankey, Henry Brem, Betty Tyler, Jordan J. Green, Eric M. JacksonAbstractTogether, medulloblastoma (MB) and atypical teratoid/rhabdoid tumors (AT/RT) represent two of the most prevalent pediatric brain malignancies. Current treatment involves radiation, which has high risks of developmental sequelae for patients under the age of three. New safer and more effective treatment modalities are needed. Cancer gene therapy is a promising alternative, but there are challenges with using viruses in pediatric patients. We developed a library of poly(beta-amino ester) (PBAE) nanoparticles and evaluated their efficacy for plasmid delivery of a suicide gene therapy to pediatric brain cancer models—specifically herpes simplex virus type I thymidine kinase (HSVtk), which results in controlled apoptosis of transfected cells. In vivo, PBAE-HSVtk treated groups had a greater median overall survival in mice implanted with AT/RT (p = 0.0083 vs. control) and MB (p 50% transfection in both cell lines tested. In vivo intracranial administration of nanoparticles carrying the HSVtk suicide gene to mice bearing orthotopic tumor xenografts significantly enhanced survival.Unlabelled Image
       
  • The humanin peptide mediates ELP nanoassembly and protects human retinal
           pigment epithelial cells from oxidative stress
    • Abstract: Publication date: Available online 23 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Zhe Li, Parameswaran G. Sreekumar, Santosh Peddi, David R. Hinton, Ram Kannan, J. Andrew MacKayAbstractHumanin (HN) is a hydrophobic 24-amino acid peptide derived from mitochondrial DNA that modulates cellular responses to oxidative stress and protects human retinal pigment epithelium (RPE) cells from apoptosis. To solubilize HN, this report describes two genetically-encoded fusions between HN and elastin-like polypeptides (ELP). ELPs provide steric stabilization and/or thermo-responsive phase separation. Fusions were designed to either remain soluble or phase separate at the physiological temperature of the retina. Interestingly, the soluble fusion assembles stable colloids with a hydrodynamic radius of 39.1 nm at 37 °C. As intended, the thermo-responsive fusion forms large coacervates (> 1,000 nm) at 37 °C. Both fusions bind human RPE cells and protect against oxidative stress-induction of apoptosis (TUNEL, caspase-3 activation). Their activity is mediated through STAT3; furthermore, STAT3 inhibition eliminates their protection. These findings suggest that HN polypeptides may facilitate cellular delivery of biodegradable nanoparticles with potential protection against age-related diseases, including macular degeneration.Graphical AbstractHumanin (HN), a 24-mer peptide of mitochondrial origin, elicits multiple cellular functions and is a potential therapeutic. When recombinantly fused to an elastin-like polypeptide (ELP), HN peptide mediates assembly of spherical nanostructures with lower critical solution behavior. These nanoparticles maintain their ability to recognize and protect human retinal pigment epithelial (RPE) cells against oxidative stress-induced apoptosis through STAT3 mediated pathway, suggesting their potential applications in ocular diseases.Unlabelled Image
       
  • Bioactive proteins delivery through core-shell nanofibers for meniscal
           tissue regeneration
    • Abstract: Publication date: Available online 4 September 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Jihye Baek, Emily Lee, Martin K Lotz, Darryl D D'LimaAbstractMimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating platelet-derived growth factor (PDGF-BB), which is a potent mitogen and chemoattractant in a core of serum albumin contained within a shell of polylactic acid. We controlled the local PDGF-BB release by adding water-soluble polyethylene glycol to the polylactic acid shell to serve as a porogen. The novel core-shell nanofibers generated 3D scaffolds with an interconnected macroporous structure, with appropriate mechanical properties and with high cell compatibility. Incorporating PDGF-BB increased cell viability, proliferation, and infiltration, and upregulated key genes involved in meniscal extracellular matrix synthesis in human meniscal and synovial cells. Our results support proof of concept that these core-shell nanofibers can create a cell-favorable nanoenvironment and can serve as a system for sustained release of bioactive factors.Graphical AbstractWe electrospun core-shell nanofibers encapsulating platelet-derived growth factor (PDGF-bb) in a core of serum albumin contained within a shell of polylactic acid. Transmission electron microscopy revealed the core of serum albumin containing PDGF-bb. Incorporating PDGF-bb increased cell viability, proliferation, and migration. Core-shell nanofibers can create a cell-favorable nanoenvironment and serve as a model system for sustained release of bioactive factors.Unlabelled Image
       
  • Tumor-specific delivery of a paclitaxel-loading HSA-haemin nanoparticle
           for cancer treatment
    • Abstract: Publication date: Available online 2 September 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Hea-Jong Chung, Hyeon-Jin Kim, Seong-Tshool HongAbstractA cancer-targeted chemotherapy could potentially eradicate cancers if anticancer drugs are delivered precisely to the cancers. Although various types of nanoparticles have been developed for cancer-specific delivery of anticancer drugs, the drug delivery capabilities of these nanoparticles were not specific enough to eradicate cancer. Here, we developed a targeting-enhancing nanoparticle of paclitaxel, in which paclitaxel was encapsulated with a human serum albumin-haemin complex through non-covalent bonding. The average diameter of TENPA was approximately 140 nm with a zeta potential of +29 mV. TENPA maintained its structural integrity and stability without forming protein coronas in the blood for optimal passive targeting. These characteristics of TENPA resulted in paclitaxel accumulation that was 4.1 times greater than that of Abraxane, an albumin-bound paclitaxel, in cancer tissue. The dramatic improvement in cancer targeting of TENPA led to reduced systemic toxicity of paclitaxel and eradication of end-stage cancer in a xenografted mouse experiment.Graphical AbstractWe developed a new concept of nanoparticle, TENPA, an encapsulated paclitaxel with albumin. To formulate TENPA, albumin is non-covalently polymerized using hemin as an adhesive agent for nanoformulation. The noncovalent albumin-hemin complex forms a very stable nanoparticle so that TENPA maintains its structural integrity and stability without forming protein corona in blood for optimal passive targeting. At the same time, albumin-hemin complex composing the shell of TENPA functioned as active targeting moieties respectively. These characteristics of TENPA contribute to reduction of toxicity and enhancement of efficacy, successfully demonstrating complete eradication of even late-stage cancer in a xenografted mouse experiment.Unlabelled Image
       
  • Recuperative effect of metformin loaded Polydopamine Nanoformulation
           promoting EZH2 mediated proteasomal degradation of phospho-α-Synuclein in
           Parkinson's disease model
    • Abstract: Publication date: Available online 31 August 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Mo. Nadim Sardoiwala, Anup K. Srivastava, Babita Kaundal, Surajit Karmakar, Subhasree Roy ChoudhuryAbstractPosttranslational modification and agglomeration of α-Synuclein (α-Syn), mitochondrial dysfunction, oxidative stress and loss of dopaminergic neurons are hallmark of Parkinson's disease (PD). This paper evaluates neuroprotection efficacy of nature inspired bio-compatible polydopamine nanocarrier for metformin delivery (Met encapsulated PDANPs) by crossing blood brain barrier in in vitro, 3D and in vivo experimental PD models. The neuroprotective potential was arbitrated by downregulation of phospho-serine 129 (pSer129) α-Syn, with reduction in oxidative stress, prevention of apoptosis and anti-inflammatory activities. The neuroprotective mechanism proved novel interaction of epigenetic regulator EZH2 mediated ubiquitination and proteasomal degradation of aggregated pSer129 α-Syn. In summary, this study divulges the neuroprotective role of Met loaded PDANPs by reversing the neurochemical deficits by confirming an epigenetic mediated nanotherapeutic approach for the PD prevention.Graphical AbstractMetformin nanoformulation [Metformin loaded Polydopamine nanoparticles] being synthesized by solution oxidation mediated self-assembly of dopamine molecules. Rotenone exposure inhibit ETC complex I of SH-SY5Y cells, thus depletion of ATP leads to simulate PD effect [In vitro PD model (1D and 3D raft PD model, PD model of mouse brain slice culture)]. Treatment of Metformin nanoformulation reduced inhibitory effects of rotenone and rescue dopaminergic neuronal cell model [SH-SY5Y cells] from apoptosis by inhibiting CASPASE3, α-Syn and 3PK and upregulating TH, DRD3, PP2A, BMI1 and novel PD associated therapeutic target EZH2. This molecular insight into the neuroprotective action of metformin nanoformulation has confirmed excellent neuroprotective potential of metformin and polydopamine nanoparticles in a signal plateform as metformin nanoformulation in treatment of PD.Unlabelled Image
       
  • RGD-functionalized magnetosomes are efficient tumor radioenhancers for
           X-rays and protons
    • Abstract: Publication date: Available online 24 August 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Maha Hafsi, Sandra Preveral, Christopher Hoog, Joel Hérault, Géraldine Adryanczyk Perrier, Christopher T Lefèvre, Hervé Michel, David Pignol, Jérôme Doyen, Thierry Pourcher, Olivier Humbert, Juliette Thariat, Béatrice CambienAbstractAlthough chemically synthesized ferro/ferrimagnetic nanoparticles have attracted great attention in cancer theranostics, they lack radio-enhancement efficacy due to low targeting and internalization ability. Herein, we investigated the potential of RGD-tagged magnetosomes, bacterial biogenic magnetic nanoparticles naturally coated with a biological membrane and genetically engineered to express an RGD peptide, as tumor radioenhancers for conventional radiotherapy and protontherapy. Although native and RGD-magnetosomes similarly enhanced radiation-induced damage to plasmid DNA, RGD-magnetoprobes were able to boost the efficacy of radiotherapy to a much larger extent than native magnetosomes both on cancer cells and in tumors. Combined to magnetosomes@RGD, protontherapy exceeded the efficacy of X-rays at equivalent doses. Also, increased secondary emissions were measured after irradiation of magnetosomes with protons versus photons. Our results indicate the therapeutic advantage of using functionalized magnetoparticles to sensitize tumors to both X-rays and protons and strengthens the case for developing biogenic magnetoparticles for multimodal nanomedicine in cancer therapy.Graphical AbstractSynthetic ferromagnetic nanoparticles are attractive cancer theranostics but lack radio-enhancement efficacy due to low targeting and internalization ability. Here we show the therapeutic advantage of using RGD-functionalized magnetosomes, biogenic ferromagnetic particles engineered to target αVβ3 integrin-positive cancer cells, in order to sensitize tumors to both X-rays and protons.Unlabelled Image
       
  • Mitochondria-targeted delocalized lipophilic cation complexed with human
           serum albumin for tumor cell imaging and treatment
    • Abstract: Publication date: Available online 24 August 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Kun Qian, Hao Chen, Chunrong Qu, Jinxu Qi, Bulin Du, Timothy Ko, Zhanhong Xiang, Martha Kandawa-Schulz, Yihong Wang, Zhen ChengAbstractSmall molecule 5BMF is a novel mitochondria-targeted delocalized lipophilic cation (DLC) with good anti-tumor activity and fluorescence emission suitable for bioimaging. In this study, human serum albumin (HSA) complexed with 5BMF (5BMF@HSA) has been developed to further improve its solubility (from 1.61 to 5.41 mg/mL), and the fluorescent intensity of 5BMF@HSA was improved over 2 times. Nearly 10-fold 5BMF was released from 5BMF@HSA complex in acidic condition when compared with neutral/basic environment. Intracellular distribution of 5BMF was altered by HSA as its signals were observed in lysosomes where free 5BMF barely localized. Both 5BMF@HSA and 5BMF showed selective toxicity toward tumor cells in μM and nM range and effectively inhibited tumor growth in mice model. In summary, 5BMF@HSA shows improved solubility in aqueous buffer and enhanced fluorescence emission, and maintains tumor inhibition capability. It is a promising protein complex for tumor cell imaging and tumor treatment.Graphical AbstractDescription: Binding 5BMF with HSA would enhance its aqueous solubility and fluorescence intensity, while still retain the small molecule's mitochondria targeting ability. Once accumulated in this organelle of cancer cells, 5BMF@HSA will disrupt mitochondria's abnormally high ΔΨm and lead to its destruction, inducing the death of cancer cells. Also, 5BMF may release from the complex in lysosomes because of the acidic environment.Unlabelled Image
       
  • pH-triggered delivery of magnetic nanoparticles depends on tumor volume
    • Abstract: Publication date: Available online 23 August 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Alexandra G. Pershina, Olga Ya. Brikunova, Alexander M. Demin, Oleg B. Shevelev, Ivan A. Razumov, Evgenii L. Zavjalov, Dina Malkeyeva, Elena Kiseleva, Nadezhda V. Krakhmal’, Sergey V. Vtorushin, Vasily L. Yarnykh, Vladimir V. Ivanov, Raisa I. Pleshko, Victor P. Krasnov, Ludmila M. OgorodovaAbstractNowadays there is growing recognition of the fact that biological systems have a greater impact on nanoparticle target delivery in tumors than nanoparticle design. Here we investigate the targeted delivery of Fe3O4 magnetic nanoparticles conjugated with pH-low-insertion peptide (MNP-pHLIP) on orthotopically induced MDA-MB-231 human breast carcinoma xenografts of varying volumes as a model of cancer progression. Using in vivo magnetic resonance imaging and subsequent determination of iron content in tumor samples by inductively coupled plasma atomic emission spectroscopy we found that MNP-pHLIP accumulation depends on tumor volume. Transmission electron microscopy, histological analysis and immunohistochemical staining of tumor samples suggest that blood vessel distribution is the key factor in determining the success of the accumulation of nanoparticles in tumors.Graphical AbstractIron oxide magnetic nanoparticles conjugated with pH-low-insertion peptide accumulated in orthotopically induced MDA-MB-231 human breast carcinoma xenografts with volume varying from 0.08 to 0.40 cm3 predominantly in dense blood vessel supply regions.Unlabelled Image
       
  • Reduction-responsive polypeptide nanomedicines significantly inhibit
           progression of orthotopic osteosarcoma
    • Abstract: Publication date: Available online 21 August 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Fei Yin, Zongyi Wang, Yafei Jiang, Tao Zhang, Zhuoying Wang, Yingqi Hua, Zhiming Song, Jianhua Liu, Weiguo Xu, Jing Xu, Zhengdong Cai, Jianxun DingAbstractOsteosarcoma (OS) is the most common malignant bone tumor with high metastasis and mortality. Neoadjuvant chemotherapy is an effective therapeutic regimen, but the clinical application is limited by the unsatisfactory efficacies and considerable side effects. In this study, the reduction-responsive polypeptide micelles based on methoxy poly(ethylene glycol)-block-poly(S-tert-butylmercapto-L-cysteine) copolymers (mPEG113-b-PBMLC4, P4M, and mPEG113-b-PBMLC9, P9M) were developed to control the delivery of doxorubicin (DOX) in OS therapy. Compared to free DOX, P4M/DOX and P9M/DOX exhibited 2.6 and 3.5 times increases in the area under the curve (AUC) of pharmacokinetics, 1.6 and 2.0 times increases in tumor accumulation, and 1.6 and 1.7 times decreases the distribution in the heart. Moreover, the selective accumulation of micelles, especially P9M/DOX, in tumors induced stronger antitumor effects on both primary and lung metastatic OSs with less systematic toxicity. These micelles with smart responsiveness to intracellular microenvironments are highly promising for the targeted delivery of clinical chemotherapeutic drugs in cancer therapy.Graphical AbstractA series of reduction-responsive polypeptide nanomedicines was developed to efficiently inhibit the growth and pulmonary metastasis of orthotopic osteosarcoma.Unlabelled Image
       
  • A pH-sensitive coordination polymer network-based nanoplatform for
           magnetic resonance imaging-guided cancer chemo-photothermal synergistic
           therapy
    • Abstract: Publication date: Available online 21 August 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Cuiting Zhang, Jing Li, Chenxi Yang, Siman Gong, Hulin Jiang, Minjie Sun, Chenggen QianAbstractDeveloping various kinds of nanoplatforms with integrated diagnostic and therapeutic functions would be significant for imaging-guided precision treatment of cancer. However, it is still a challenge to organically integrate therapeutic and imaging components into a single nano-system rather than simply mixing. Herein, an iron-gallic acid network-based nanoparticle (Fe-GA@PEG-PLGA) was designed for magnetic resonance imaging (MRI)-guided chemo-photothermal synergistic therapy of tumors. The tumor spatial location and size information can be accurately achieved due to T1 MRI based on Fe3+ coordination with GA in Fe-GA network. Furthermore, the nanoparticle exhibited extraordinary photostability and photothermal therapy capacity exceeded 42 °C within 100 s under 808 nm laser irradiation. Meanwhile, the Fe-GA polymeric network can be disassembled in tumor acidic environment and the released drug GA can induce apoptosis. This study demonstrated that the Fe-GA network-based nanoparticle is a promising diagnostic and therapeutic agent for theranostic application and further clinic translation.Graphical AbstractIllustration of a multifunctional iron-gallic acid (Fe-GA) network-based nanoparticle as a theranostic agent for magnetic resonance imaging-guided photothermal therapy and chemotherapy. The results suggest that Fe-GA network-based nanoplatform is safe and practical, and can effectively kill tumor cells under chemo-photothermal synergistic therapy.Unlabelled Image
       
  • Noncovalent tethering of nucleic acid aptamer on DNA nanostructure for
           targeted photo/chemo/gene therapies
    • Abstract: Publication date: Available online 22 July 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Gayong Shim, Jinwon Park, Mi-Gyeong Kim, Geon Yang, Yeon Lee, Yu-Kyoung OhHere, we report various therapeutic cargo-loadable DNA nanostructures that are shelled in polydopamine and noncovalently tethered with cancer cell-targeting DNA aptamers. Initial DNA nanostructure was formed by rolling-circle amplification and condensation with Mu peptides. This DNA nanostructure was loaded with an antisense oligonucleotide, a photosensitizer, or an anticancer chemotherapeutic drug. Each therapeutic agent-loaded DNA nanostructure was then shelled with polydopamine (PDA), and noncovalently decorated with a poly adenine-tailed nucleic acid aptamer (PA) specific for PTK7 receptor, resulting in PA-tethered and PDA-shelled DNA nanostructure (PA/PDN). PDA coating shell enabled photothermal therapy. In the cells overexpressing PTK7 receptor, photosensitizer-loaded PA/PDN showed greater photodynamic activity. Doxorubicin-loaded PA/PDN exerted higher anticancer activity than the other groups. Antisense oligonucleotide-loaded PA/PDN provided selective reduction of target proteins compared with other groups. Our results suggest that the PA-tethered and PDA-shelled DNA nanostructures could enable the specific receptor-targeted phototherapy, chemotherapy, and gene therapy against cancer cells.Graphical abstractDNA nanostructures with various cargoes were shelled with polydopamine and noncovalently tethered with nucleic acid aptamer. The nanostructures enable specific receptor-targeted photo/chemo and gene therapies.Unlabelled Image
       
  • Corrigendum to “A rationally designed photo-chemo core-shell
           nanomedicine for inhibiting the migration of metastatic breast cancer
           cells followed by photodynamic killing” [nanomedicine, 10(3):579–87]
    • Abstract: Publication date: Available online 21 June 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Giridharan Loghanathan Malarvizhi, Parwathy Chandran, Archana Payickattu Retnakumari, Ranjith Ramachandran, Neha Gupta, Shantikumar Nair, Manzoor Koyakutty
       
 
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