Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin®) conjugated polyethylenimine

Shih Jiuan Chiu, Naoto T. Ueno, Robert J. Lee

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

A series of novel nonviral vectors targeting the HER-2/neu gene product human epidermal growth factor receptor-2 (HER2) were constructed and evaluated in breast cancer cell lines to optimize vector formulation for receptor-specific gene transfer. These vectors were DNA/polycation complexes (polyplexes) prepared by mixing, at varying ratios, plasmid DNA carrying a luciferase reporter gene to HerPEI, which is a conjugate of linear polyethylenimine (PEI), a cationic polymer, and trastuzumab (Herceptin®), a HER2-specific monoclonal antibody. Transfection studies were carried out in both HER2 overexpressing Sk-Br-3 and HER2 low-expressing MDA-MB-231 breast cancer cells. The HerPEI polyplexes showed significantly greater transfection activity up to 20-folds than nonderivatized PEI-based polyplexes in the Sk-Br-3 cells. The transfection efficiency of targeted polyplexes was dependent on the trastuzumab:PEI ratio and can be blocked by excess free trastuzumab, suggesting HER2-mediated gene delivery. In contrast, no significant difference in transfection activities was observed between HER2-targeted and nontargeted polyplexes in the HER2 low-expressing MDA-MB-231 cells. The transfection efficiency of HerPEI polyplexes was retained in serum-containing medium. In summary, HerPEI polyplexes have shown promising HER2 receptor-specific gene transfer properties and warrant further evaluation as a tumor-targeted vector for gene therapy.

Original languageEnglish
Pages (from-to)357-369
Number of pages13
JournalJournal of Controlled Release
Volume97
Issue number2
DOIs
Publication statusPublished - Jun 18 2004
Externally publishedYes

Keywords

  • Drug targeting
  • Gene therapy
  • HER-2/neu
  • HER2 receptor
  • Nonviral gene transfer vectors
  • Polyethylenimine
  • Trastuzumab

ASJC Scopus subject areas

  • Pharmaceutical Science

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