Pigment epithelium-derived factor gene loaded in cRGD-PEG-PEI suppresses colorectal cancer growth by targeting endothelial cells

Lei Li, Jun Yang, Wei Wei Wang, Ya Chao Yao, Shu Huan Fang, Zhi Yu Dai, Hong Hai Hong, Xia Yang, Xin Tao Shuai, Guo Quan Gao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Pigment epithelium-derived factor (PEDF) recombinant protein has been investigated in many kinds of solid tumors due to its potent antiangiogenic activity. However, the complexity of protein purification, instability of recombinant protein and requirement of repeated injections are obstacles for the recombinant PEDF therapy for solid tumors. We successfully synthesized polyethyleneglycol-polyetherimide (PEG-PEI) and cRGD-PEG-PEI which was coupled with a cyclic RGD peptide, a special ligand for integrin αvβ3 receptor, as the vehicle for PEDF gene therapy in this study. In vitro, the competitive binding assay showed that cRGD contributed to the enhanced gene transfection efficiency of PEG-PEI in human umbilical vein endothelial cells (HUVECs). PEDF gene delivered by cRGD-PEG-PEI apparently suppressed growth of tumor with a 67.4% reduction and decreased microvessel density in nude mice bearing SW620 human colorectal xenografts. Accordingly, SW620 tumors from cRGD-PEG-PEI/PEDF-pcDNA3.1 (+)-treated mice expressed more PEDF than that of the control groups. Our study demonstrated that cRGD-PEG-PEI transported the PEDF gene into endothelia cells more efficiently than PEG-PEI, resulting in more effective inhibitory effects on tumor growth by anti-angiogenesis. Therefore, for the first time, we have explored an effective non-viral vehicle for PEDF gene therapy by targeting endothelial cells.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume438
Issue number1-2
DOIs
StatePublished - Nov 15 2012

Keywords

  • Gene therapy
  • HUVECs
  • PEDF
  • PEG-PEI
  • cRGD

ASJC Scopus subject areas

  • Pharmaceutical Science

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