The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain

Rongqin Huang, Weilun Ke, Yang Liu, Chen Jiang, Yuanying Pei

Research output: Contribution to journalArticle

Abstract

Development of an efficient gene vector is a key-limiting factor of brain gene therapy. In this study, lactoferrin (Lf), for the first time, was investigated as a brain-targeting ligand in the design of polyamidoamine (PAMAM)-based non-viral gene vector to the brain. Using polyethyleneglycol (PEG) as a spacer, PAMAM-PEG-Lf was successfully synthesized. This vector showed a concentration-dependent manner in the uptake in brain capillary endothelial cells (BCECs). The brain uptake of PAMAM-PEG-Lf was 2.2-fold compared to that of PAMAM-PEG-transferrin (Tf) in vivo. The transfection efficiency of PAMAM-PEG-Lf/DNA complex was higher than that of PAMAM-PEG-Tf/DNA complex in vitro and in vivo. The results of frozen sections showed the widespread expression of an exogenous gene in mouse brain via intravenous administration. With a PAMAM/DNA weight ratio of 10:1, the brain gene expression of the PAMAM-PEG-Lf/DNA complex was about 2.3-fold when compared to that of the PAMAM-PEG-Tf/DNA complex. These results provide evidence that PAMAM-PEG-Lf can be exploited as a potential non-viral gene vector targeting to the brain via noninvasive administration. Lf is a promising ligand for the design of gene delivery systems targeting to the brain.

Original languageEnglish (US)
Pages (from-to)238-246
Number of pages9
JournalBiomaterials
Volume29
Issue number2
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Keywords

  • Brain targeting
  • Lactoferrin
  • Polyamidoamine
  • Receptor-mediated gene delivery

ASJC Scopus subject areas

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

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