Insight on the fate of CNS-targeted nanoparticles. Part II: Intercellular neuronal cell-to-cell transport

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• 作者：Giovanni Tosi^a ; Antonietta Vilella^b ; Resham Chhabra^c ; Michael J. Schmeisser^d ; Tobias M. Boeckers^d ; Barbara Ruozi^a ; Maria Angela Vandelli^a ; Flavio Forni^a ; Michele Zoli^b ; Andreas M. Grabrucker^c ; ^d ; ^{andreas.grabrucker@uni-ulm.de" class="auth_mail}
• 关键词：g7-NPs ; M-Sec ; Neuron ; Tunneling nanotubes ; TNT
• 刊名：Journal of Controlled Release
• 出版年：10 March, 2014
• 年：2014
• 卷：177
• 期：Complete
• 页码：96-107
• 全文大小：1958 K

文摘

The application of polymeric nanoparticles (NPs) has a promising future for targeting and delivering drugs into the central nervous system (CNS). However, the fate of NPs once entered in the brain after crossing the blood-brain barrier (BBB) and taken up into neuronal cells is a neglected area of study. Thus, here, we investigate the possible mechanisms of a cell-to-cell transport of poly-lactide-co-glycolide (PLGA) NPs modified with a glycopeptide (g7-NPs), already demonstrated to be able to cross the BBB after in vivo administration in rodents. We also tested antibody (Ab) -modified g7-NPs both in vitro and in vivo to investigate the possibility of specific targeting. Our results show that g7-NPs can be transported intra- and inter-cellularly within vesicles after vesicular internalization. Moreover, cell-to-cell transport is mediated by tunneling-nanotube (TNT)-like structures in cell lines and most interestingly in glial as well as neuronal cells in vitro. The transport is dependent on F-actin and can be increased by induction of TNT-like structures overexpressing M-Sec, a central factor and inducer of TNT formation. Moreover, cell-to-cell transport occurs independently from NP surface modification with antibodies. These in vitro findings were in part confirmed by in vivo evidence after i.p. administration of NPs in mice.