Insight on the fate of CNS-targeted nanoparticles. Part I: Rab5-dependent cell-specific uptake and distribution

Antonietta Vilella, Giovanni Tosi, Andreas M. Grabrucker, Barbara Ruozi, Daniela Belletti, Maria Angela Vandelli, Tobias M. Boeckers, Flavio Forni, Michele Zoli

Research output: Contribution to journalArticlepeer-review

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. In this paper, 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. Our results show that in vivo administration of g7-NPs leads to a region- and cell type-specific enrichment of NPs within the brain. 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 can be promising carriers for the treatment of neuropsychiatric and neurodegenerative diseases.

Original languageEnglish
Pages (from-to)195-201
Number of pages7
JournalJournal of Controlled Release
Volume174
Issue number1
DOIs
Publication statusPublished - 28 Jan 2014
Externally publishedYes

Keywords

  • CNS targeting
  • Distribution
  • Nanoparticles
  • Neuronal uptake

Fingerprint

Dive into the research topics of 'Insight on the fate of CNS-targeted nanoparticles. Part I: Rab5-dependent cell-specific uptake and distribution'. Together they form a unique fingerprint.

Cite this