D-SP5 Peptide-Modified Highly Branched Polyethylenimine for Gene Therapy of Gastric Adenocarcinoma
D-SP5 Peptide-Modified Highly Branched Polyethylenimine for Gene Therapy of Gastric Adenocarcinoma
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DOI：
10.1021/acs.bioconjchem.5b00137
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发表时间：
2015-08-01
影响因子：
4.7
通讯作者：
Liu, Min
中科院分区：
文献类型：
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作者：
Li, Xue;Xie, Zuoxu;Liu, Min
肽介导的肿瘤靶向治疗已成为肿瘤治疗的有效策略。反转肽抵抗蛋白酶降解并保持其生物活性。我们利用反转录肽（D）（PRPSPKMGVSVS）（D-SP 5）作为靶向配体，开展胃腺癌的基因治疗。D-SP 5与人胃腺癌细胞（SGC 7901）的亲和力高于其亲本肽（L）（SVSVGMKPSPRP）（L-SP 5）。制备了聚乙烯亚胺（PEI）/pDNA、聚乙二醇（mPEG）-PEI/pDNA和D-SP 5-PEG-PEI/pDNA用于进一步研究。荧光素酶定量检测结果显示，D-SPS-PEG-PEI/pGL的转染效率（4.2）高于mPEG-PEI/pGL（4.2）。流式细胞仪检测发现，D-SP 5-PEG-PEI/pTRAIL处理的胃癌细胞凋亡率高于mPEG-PEI/pTRAIL处理的胃癌细胞。Western blot结果显示，D-SP 5-PEG-PEI/pTRAIL处理的胃癌细胞系SGC 7901中肿瘤坏死因子相关凋亡诱导配体（tumor necrosis factor-related apoptosis inducing ligand，TRAIL）蛋白的表达明显高于mPEG-PEI/pTRAIL处理的胃癌细胞系SGC 7901。体内药效学研究表明，D-SP 5-PEG-PEI/pTRAIL对胃癌SGC 7901裸鼠移植瘤的生长有抑制作用。结果表明，D-SP 5-PEG-PEI是一种安全、高效的基因载体，在抗肿瘤基因治疗中具有潜在的应用价值。
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-SPS-PEG-PEI/pGL(4.2) was larger compared with that of mPEG-PEI/pGL(4.2). 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.