D-SP5 Peptide-Modified Highly Branched Polyethylenimine for Gene Therapy of Gastric Adenocarcinoma
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- 作者：Xue Li ; Zuoxu Xie ; Cao Xie ; Weiyue Lu ; Chunli Gao ; Henglei Ren ; Man Ying ; Xiaoli Wei ; Jie Gao ; Bingxia Su ; Yachao Ren ; Min Liu
- 刊名：Bioconjugate Chemistry
- 出版年：2015
- 出版时间：August 19, 2015
- 年：2015
- 卷：26
- 期：8
- 页码：1494-1503
- 全文大小：536K
- ISSN：1520-4812
文摘
Peptide-mediated targeting of tumors has become an effective strategy for cancer therapy. Retro-inverso peptides resist protease degradation and maintain their bioactivity. We used the retro-inverso peptide D(PRPSPKMGVSVS) (D-SP5) as a targeting ligand to develop gene therapy for gastric adenocarcinoma. D-SP5 has a higher affinity for human gastric adenocarcinoma (SGC7901) cells compared with that of its parental peptide, L(SVSVGMKPSPRP) (L-SP5). Polyethylenimine (PEI)/pDNA, polyethylene glycol (mPEG)-PEI/pDNA and D-SP5-PEG-PEI/pDNA were prepared for further study. Quantitative luciferase assays showed the transfection efficiency of D-SP5-PEG-PEI/pGL4.2 was larger compared with that of mPEG-PEI/pGL4.2. Flow cytometry assays revealed that the apoptosis rates of SGC7901 cells treated with D-SP5-PEG-PEI/pTRAIL were larger than mPEG-PEI/pTRAIL. Western blot assays indicated that the expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) protein in SGC7901 cells treated with D-SP5-PEG-PEI/pTRAIL was higher compared with that in cells treated with mPEG-PEI/pTRAIL. In vivo pharmacodynamics study revealed that D-SP5-PEG-PEI/pTRAIL could inhibit the growth of gastric adenocarcinoma SGC7901 xenografts in nude mice. Our results demonstrate that D-SP5-PEG-PEI is a safe and efficient gene delivery vector with potential applications in antitumor gene therapy.