Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles

Yang Liu, Rongqin Huang, Liang Han, Weilun Ke, Kun Shao, Liya Ye, Jinning Lou, Chen Jiang

Research output: Contribution to journalArticlepeer-review

Abstract

A 29 amino-acid peptide derived from the rabies virus glycoprotein (RVG29) was exploited as a ligand for efficient brain-targeting gene delivery. RVG29 was modified on polyamidoamine dendrimers (PAMAM) through bifunctional PEG, then complexed with DNA, yielding PAMAM-PEG-RVG29/DNA nanoparticles (NPs). The NPs were observed to be uptaken by brain capillary endothelial cells (BCECs) through a clathrin and caveolae mediated energy-depending endocytosis. The specific cellular uptake can be inhibited by free RVG29 and GABA but not by nicotinic acetylcholine receptor (nAchR) agonists/antagonists, indicating RVG29 probably relates to the GABAB receptor besides nAchR reported previously. PAMAM-PEG-RVG29/DNA NPs showed higher blood-brain barrier (BBB)-crossing efficiency than PAMAM/DNA NPs in an in vitro BBB model. In vivo imaging showed that the NPs were preferably accumulated in brain. The report gene expression of the PAMAM-PEG-RVG29/DNA NPs was observed in brain, and significantly higher than unmodified NPs. Thus, PAMAM-PEG-RVG29 provides a safe and noninvasive approach for the gene delivery across the BBB.

Original languageEnglish (US)
Pages (from-to)4195-4202
Number of pages8
JournalBiomaterials
Volume30
Issue number25
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Keywords

  • Brain targeting
  • GABA receptor
  • Gene delivery
  • Non-viral vector
  • Polyamidoamine
  • RVG

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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