Employment of brain-targeted nanocarriers as tools for drug delivery to the central nervous system (CNS) represents a pivotal step forward in the development of innovative therapeutic strategies. If nanocarriers are to be translated into the clinic, their distribution within the brain and interaction with CNS cells must be assessed accurately. Here, we investigated these issues by employing polylactide-co-glycolide nanoparticles (NPs) specifically engineered with g7, a glycopeptide conferring the ability to cross the blood brain barrier (BBB) at a concentration of up to 10% of the injected dose. g7-NPs display increased in vitro uptake in neurons and glia. Our results show that in vivo administration of g7-NPs leads to a region- and cell type-specific enrichment of NPs within the brain that is not dependent on the presence of the BBB. We provide evidence that g7-NPs are endocytosed in a clathrin-dependent manner and transported into a specific subset of early endosomes positive for Rab5 in vitro and in vivo. The differential Rab5 expression level is strictly correlated with the amount of g7-NP accumulation. These findings show that g7-NPs can cross the BBB and target specific brain cell populations, suggesting that these NPs are promising drug carriers for the treatment of neuropsychiatric diseases.

Rab5-dependent cell-specific uptake and distribution of engineered nanoparticles for CNS targeted drug delivery in vivo / Vilella, Antonietta; Tosi, Giovanni; Grabrucker, A. M.; Ruozi, Barbara; Belletti, Daniela; Vandelli, Maria Angela; Boeckers, T. M.; Forni, Flavio; Zoli, Michele. - STAMPA. - 1:(2013), pp. 1-1. ((Intervento presentato al convegno XV CONGRESS OF THE ITALIAN SOCIETY OF NEUROSCIENCE tenutosi a Roma nel 3.10.2013-5.10.2013.

Rab5-dependent cell-specific uptake and distribution of engineered nanoparticles for CNS targeted drug delivery in vivo

VILELLA, ANTONIETTA;TOSI, Giovanni;RUOZI, Barbara;BELLETTI, Daniela;VANDELLI, Maria Angela;FORNI, Flavio;ZOLI, Michele
2013

Abstract

Employment of brain-targeted nanocarriers as tools for drug delivery to the central nervous system (CNS) represents a pivotal step forward in the development of innovative therapeutic strategies. If nanocarriers are to be translated into the clinic, their distribution within the brain and interaction with CNS cells must be assessed accurately. Here, we investigated these issues by employing polylactide-co-glycolide nanoparticles (NPs) specifically engineered with g7, a glycopeptide conferring the ability to cross the blood brain barrier (BBB) at a concentration of up to 10% of the injected dose. g7-NPs display increased in vitro uptake in neurons and glia. Our results show that in vivo administration of g7-NPs leads to a region- and cell type-specific enrichment of NPs within the brain that is not dependent on the presence of the BBB. We provide evidence that g7-NPs are endocytosed in a clathrin-dependent manner and transported into a specific subset of early endosomes positive for Rab5 in vitro and in vivo. The differential Rab5 expression level is strictly correlated with the amount of g7-NP accumulation. These findings show that g7-NPs can cross the BBB and target specific brain cell populations, suggesting that these NPs are promising drug carriers for the treatment of neuropsychiatric diseases.
XV CONGRESS OF THE ITALIAN SOCIETY OF NEUROSCIENCE
Roma
3.10.2013-5.10.2013
Vilella, Antonietta; Tosi, Giovanni; Grabrucker, A. M.; Ruozi, Barbara; Belletti, Daniela; Vandelli, Maria Angela; Boeckers, T. M.; Forni, Flavio; Zoli, Michele
Rab5-dependent cell-specific uptake and distribution of engineered nanoparticles for CNS targeted drug delivery in vivo / Vilella, Antonietta; Tosi, Giovanni; Grabrucker, A. M.; Ruozi, Barbara; Belletti, Daniela; Vandelli, Maria Angela; Boeckers, T. M.; Forni, Flavio; Zoli, Michele. - STAMPA. - 1:(2013), pp. 1-1. ((Intervento presentato al convegno XV CONGRESS OF THE ITALIAN SOCIETY OF NEUROSCIENCE tenutosi a Roma nel 3.10.2013-5.10.2013.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/974305
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