Development of novel Zn2+ loaded Nanoparticles designed for cell-type targeted drug release in CNS neurons: In vitro evidences

Andreas M. Grabrucker, Craig C. Garner, Tobias M. Boeckers, Lucia Bondioli, Barbara Ruozi, Flavio Forni, Maria Angela Vandelli, Giovanni Tosi

Research output: Contribution to journalArticlepeer-review

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 Zn2+ 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 Zn2+. 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 Zn2+ to the CNS and thus a means to explore the influence of altered zinc levels linked to neuropsychological disorders such as depression.

Original languageEnglish
Article numbere17851
Pages (from-to)e17851
JournalPLoS ONE
Volume6
Issue number3
DOIs
Publication statusPublished - 2011
Externally publishedYes

Fingerprint

Dive into the research topics of 'Development of novel Zn2+ loaded Nanoparticles designed for cell-type targeted drug release in CNS neurons: In vitro evidences'. Together they form a unique fingerprint.

Cite this