Follicle stimulating hormone receptor mediated gene delivery to target ovarian carcinoma in vitro
Follicle stimulating hormone receptor mediated gene delivery to target ovarian carcinoma in vitro
复制标题
卵泡刺激素受体介导的体外基因递送靶向卵巢癌
DOI：
10.5372/1905-7415.0602.045
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发表时间：
2012-04-01
影响因子：
0.6
通讯作者：
Xu, Congjian
中科院分区：
文献类型：
--
作者：
Dong, Chris;Chen, Jun;Xu, Congjian
摘要背景：如何将足够的治疗基因导入癌细胞，同时减少副作用是癌症基因治疗的主要挑战。受体介导的基因递送使得能够将治疗基因特异性递送到靶癌细胞中并增加功效。目的：我们开发了一种新的受体介导的短干扰RNA（siRNA）表达质粒载体系统，在体外对卵巢癌细胞具有更好的生物相容性。研究方法：将卵泡刺激素（FSH）肽（β：33-55）通过双功能聚乙二醇（PEG）接枝到聚乙烯亚胺（PEI）上，并与抗趋化因子c-x-c基序配体1（CXCL 1）质粒DNA（pDNA）复合，形成不同N/P比的FSH-PEG-PEI/pDNA复合物。分别检测转染细胞的细胞毒活性、转染效率和CXCL 1沉默效果。结果：FSH-PEG-PEI/pDNA复合物具有低细胞毒性、高转染效率和特异性CXCL 1基因沉默作用。当N/P比为25时，2% FSH-PEG-PEI与pDNA复合物的理化性质较好。表达卵泡刺激素受体（FSHR）的卵巢癌细胞通过受体介导的方式摄取治疗性siRNA表达质粒。结论：FSH-PEG-PEI偶联物可作为一种新型的受体介导的抗卵巢癌基因传递系统。这种策略可以扩展到针对不同癌症的广泛的靶向基因治疗。
Abstract Background: How to deliver sufficient therapeutic genes into cancer cells while causing fewer side effects are major challenges in cancer gene therapies. Receptor mediated gene delivery enables specific delivering therapeutic genes into target cancer cells and increases the efficacy. Objectives: We developed a novel receptor mediated short interference RNA (siRNA) expression plasmid delivery system against ovarian carcinoma cells with improved biocompatibility in vitro. Methods: Follice stimulating hormone (FSH) peptide (β: 33-55) was grafted to polyethylenimine (PEI) via a bifunctional polyethylene glycol (PEG) and complexed with anti chemokine c-x-c motif ligand 1 (CXCL1) plasmid DNA (pDNA) to form FSH-PEG-PEI/pDNA polyplexes at various N/P ratios. The cytotocity, transfection efficiency, and CXCL1 silencing effect were evaluated respectively. Results: The FSH-PEG-PEI/pDNA polyplexes showed low cytotoxicity, high transfection efficiency, and specific CXCL1 gene silencing effect. The 2% FSH-PEG-PEI conjugate complexed with pDNA at N/P ratio of 25 has better physicochemical properties. The therapeutic siRNA expression plasmid uptake by follice stimulating hormone receptor (FSHR) expression ovarian carcinoma cells was through a receptor-mediated manner. Conclusion: The FSH-PEG-PEI conjugate can be used as a novel receptor mediated gene delivery system against ovarian carcinomas. This strategy could be extended to a wide range of targeted gene therapeutics against different cancers.