Nanocarriers can be useful tools for delivering drugs to the central nervous system (CNS). Their distribution within the brain and their interaction with CNS cells must be assessed accurately before they can be proposed for therapeutic use. We investigated these issues by employing poly-lactide-co- glycolide nanoparticles (NPs) specifically engineered with a glycopeptide (g7) conferring to NPs 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 glial cells, in vivo administration of g7-NPs leads to a region- And cell type-specific enrichment of NPs within the brain. Moreover, 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. Moreover, in order to understand the journey of NPs, we demonstrated that g7-NPs can be transported intra- And intercellularly inside vesicles. 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. These in vitro findings were in part confirmed by in vivo evidence after i.p. administration in mice. We also tested Ab-modified g7-NPs both in vitro and in vivo to investigate the possibility of a specific targeting.
Nanomedicine in neurodegenerative disorders: Understanding the journey / Tosi, G.; Ruozi, B.; Vilella, A.; Grabrucker, A. M.; Belletti, D.; Vandelli, M. A.; Boeckers, T. M.; Forni, F.; Zoli, M.; Sharma, A.; Muresanu, D. F.; Sharma, H. S.. - 3:(2015), pp. 25-28. (Intervento presentato al convegno 10th Annual TechConnect World Innovation Conference and Expo, Held Jointly with the 18th Annual Nanotech Conference and Expo, and the 2015 National SBIR/STTR Conference tenutosi a usa nel 2015).
Nanomedicine in neurodegenerative disorders: Understanding the journey
Tosi G.;Ruozi B.;Vilella A.;Belletti D.;Vandelli M. A.;Forni F.;Zoli M.;
2015
Abstract
Nanocarriers can be useful tools for delivering drugs to the central nervous system (CNS). Their distribution within the brain and their interaction with CNS cells must be assessed accurately before they can be proposed for therapeutic use. We investigated these issues by employing poly-lactide-co- glycolide nanoparticles (NPs) specifically engineered with a glycopeptide (g7) conferring to NPs 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 glial cells, in vivo administration of g7-NPs leads to a region- And cell type-specific enrichment of NPs within the brain. Moreover, 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. Moreover, in order to understand the journey of NPs, we demonstrated that g7-NPs can be transported intra- And intercellularly inside vesicles. 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. These in vitro findings were in part confirmed by in vivo evidence after i.p. administration in mice. We also tested Ab-modified g7-NPs both in vitro and in vivo to investigate the possibility of a specific targeting.
Pubblicazioni consigliate
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris
