A leptin derived 30-amino-acid peptide modified pegylated poly-l-lysine dendrigraft for brain targeted gene delivery

Yang Liu, Jianfeng Li, Kun Shao, Rongqin Huang, Liya Ye, Jinning Lou, Chen Jiang

Research output: Contribution to journalArticle

Abstract

The blood-brain barrier is the major obstacle that prevents diagnostic and therapeutic drugs being delivered to the central nervous systems in order to exert their effects. Specific ligand-receptor binding mediated endocytosis is one of the possible strategies to cross this barrier. A 30-amino-acid peptide (leptin30) derived from an endogenic hormone-leptin is exploited as brain-targeting ligand as it is reported to possess the same brain accumulation efficiency after intravenous injection. Dendrigraft poly-l-lysine (DGL) is used as non-viral gene vector in this study. DGL-PEG-Leptin30 was complexed with plasmid DNA yielding nanoparticles (NPs). The cellular uptake characteristic and mechanism were explored in brain capillary endothelial cells (BCECs) which express leptin receptors. Furthermore, brain parenchyma microglia cells such as BV-2 cells expressing leptin receptors could promote ligand-receptor mediated endocytosis leading to enhanced gene transfection ability of DGL-PEG-Leptin30/DNA NPs. The targeted NPs were proved to be transported across in vitro BBB model effectively and accumulate more in brains after i.v. resulting in a relatively high gene transfection efficiency both in vitro and in vivo. Besides, the NPs showed low cytotoxicity after in vitro transfection. Thus, DGL-PEG-Leptin30 provides a safe and noninvasive approach for the delivery of gene across the blood-brain barrier.

Original languageEnglish (US)
Pages (from-to)5246-5257
Number of pages12
JournalBiomaterials
Volume31
Issue number19
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

Keywords

  • Brain targeting
  • Dendrigraft poly-l-lysine
  • Gene delivery
  • Leptin
  • Non-viral vector

ASJC Scopus subject areas

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

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