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 a specific targeting. Our results show that g7-NPs can be transported intra- and intercellularly inside vesicles. 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 in mice.

Insight on the fate of CNS-targeted nanoparticles. Part II: Intercellular neuronal cell-to-cell transport / Tosi, Giovanni; Vilella, Antonietta; Resham, Chhabra; Michael J., Schmeisser; Tobias M., Boeckers; Ruozi, Barbara; Vandelli, Maria Angela; Forni, Flavio; Zoli, Michele; Andreas M., Grabrucker. - In: JOURNAL OF CONTROLLED RELEASE. - ISSN 0168-3659. - STAMPA. - 177:(2014), pp. 96-107. [10.1016/j.jconrel.2014.01.004]

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

TOSI, Giovanni;VILELLA, ANTONIETTA;RUOZI, Barbara;VANDELLI, Maria Angela;FORNI, Flavio;ZOLI, Michele;
2014

Abstract

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 a specific targeting. Our results show that g7-NPs can be transported intra- and intercellularly inside vesicles. 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 in mice.
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96
107
Insight on the fate of CNS-targeted nanoparticles. Part II: Intercellular neuronal cell-to-cell transport / Tosi, Giovanni; Vilella, Antonietta; Resham, Chhabra; Michael J., Schmeisser; Tobias M., Boeckers; Ruozi, Barbara; Vandelli, Maria Angela; Forni, Flavio; Zoli, Michele; Andreas M., Grabrucker. - In: JOURNAL OF CONTROLLED RELEASE. - ISSN 0168-3659. - STAMPA. - 177:(2014), pp. 96-107. [10.1016/j.jconrel.2014.01.004]
Tosi, Giovanni; Vilella, Antonietta; Resham, Chhabra; Michael J., Schmeisser; Tobias M., Boeckers; Ruozi, Barbara; Vandelli, Maria Angela; Forni, Flavio; Zoli, Michele; Andreas M., Grabrucker
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/994517
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