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Insight on the fate of CNS-targeted nanoparticles. Part II: Intercellular neuronal cell-to-cell transport.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2014 Mar 10; Vol. 177, pp. 96-107. Date of Electronic Publication: 2014 Jan 11. - Publication Year :
- 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 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.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Animals, Newborn
Antibodies administration & dosage
Antibodies chemistry
Biological Transport
COS Cells
Cells, Cultured
Chlorocebus aethiops
Embryo, Mammalian
Glycopeptides chemistry
Hippocampus cytology
Hyaluronan Receptors immunology
Lactic Acid chemistry
Mice, Inbred C57BL
Nanoparticles chemistry
Neural Cell Adhesion Molecules immunology
Neuroglia metabolism
Polyglycolic Acid chemistry
Polylactic Acid-Polyglycolic Acid Copolymer
Rats
Rats, Sprague-Dawley
Glycopeptides administration & dosage
Lactic Acid administration & dosage
Nanoparticles administration & dosage
Neurons metabolism
Polyglycolic Acid administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 177
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 24417968
- Full Text :
- https://doi.org/10.1016/j.jconrel.2014.01.004