title: Development of novel Zn2+ loaded nanoparticles designed for cell-type targeted drug release in CNS neurons: in vitro evidences.
abstract: Intact synaptic function and plasticity are fundamental prerequisites to a healthy brain. Therefore, synaptic proteins are one of the major targets for drugs used as neuro-chemical therapeutics. Unfortunately, the majority of drugs is not able to cross the blood-brain barrier (BBB) and is therefore distributed within the CNS parenchyma. Here, we report the development of novel biodegradable Nanoparticles (NPs), made of poly-lactide-co-glycolide (PLGA) conjugated with glycopeptides that are able to cross the BBB and deliver for example Zn(2+) ions. We also provide a thorough characterization of loaded and unloaded NPs for their stability, cellular uptake, release properties, toxicity, and impact on cell trafficking. Our data reveal that these NPs are biocompatible, and can be used to elevate intracellular levels of Zn(2+). Importantly, by engineering the surface of NPs with antibodies against NCAM1 and CD44, we were able to selectively target neurons or glial cells, respectively. Our results indicate that these biodegradable NPs provide a potential new venue for the delivery Zn(2+) to the CNS and thus a means to explore the influence of altered zinc levels linked to neuropsychological disorders such as depression.
authors: Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford University, Stanford, California, United States of America. andreas.grabrucker@stanford.edu
authors: Andreas M
authors: AM
authors: Grabrucker
authors: Craig C
authors: CC
authors: Garner
authors: Tobias M
authors: TM
authors: Boeckers
authors: Lucia
authors: L
authors: Bondioli
authors: Barbara
authors: B
authors: Ruozi
authors: Flavio
authors: F
authors: Forni
authors: Maria Angela
authors: MA
authors: Vandelli
authors: Giovanni
authors: G
authors: Tosi
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009024:Morphogenesis / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015032:Zinc / Q000737:chemistry*
chemical_list: D015032:Zinc