Yang Yi, Zhao Hang, Jia YanPeng, Guo QingFa, Qu Ying, Su Jing, Lu XiaoLing, Zhao YongXiang, Qian ZhiYong
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China.
National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, 22 Shuang Yong Rd. Nanning, Guangxi 530021, China.
Sci Rep. 2016 Feb 17;6:21402. doi: 10.1038/srep21402.
Local anti-oncogene delivery providing high local concentration of gene, increasing antitumor effect and decreasing systemic side effects is currently attracting interest in cancer therapy. In this paper, a novel local sustained anti-oncogene delivery system, PECE thermoresponsive hydrogel containing folate-poly (ester amine) (FA-PEA) polymer/DNA (tumor suppressor) complexes, is demonstrated. First, a tumor-targeted biodegradable folate-poly (ester amine) (FA-PEA) polymer based on low-molecular-weight polyethyleneimine (PEI) was synthesized and characterized, and the application for targeted gene delivery was investigated. The polymer had slight cytotoxicity and high transfection efficiency in vitro compared with PEI 25k, which indicated that FA-PEA was a potential vector for targeted gene delivery. Meanwhile, we successfully prepared a thermoresponsive PECE hydrogel composite containing FA-PEA/DNA complexes which could contain the genes and slowly release the genes into cells. We concluded the folate-poly (ester amine) (FA-PEA) polymer would be useful for targeted gene delivery, and the novel gene delivery composite based on biodegradable folate-poly (ester amine) polymer and thermosensitive PECE hydrogel showed potential for sustained gene release.
局部抗癌基因递送可提供高局部基因浓度,增强抗肿瘤效果并降低全身副作用,目前在癌症治疗中备受关注。本文展示了一种新型的局部持续抗癌基因递送系统,即含有叶酸 - 聚(酯胺)(FA - PEA)聚合物/DNA(肿瘤抑制因子)复合物的PECE温敏水凝胶。首先,合成并表征了一种基于低分子量聚乙烯亚胺(PEI)的肿瘤靶向可生物降解叶酸 - 聚(酯胺)(FA - PEA)聚合物,并研究了其在靶向基因递送中的应用。与PEI 25k相比,该聚合物在体外具有轻微的细胞毒性和高转染效率,这表明FA - PEA是一种潜在的靶向基因递送载体。同时,我们成功制备了一种含有FA - PEA/DNA复合物的温敏PECE水凝胶复合材料,该材料可包载基因并将其缓慢释放到细胞中。我们得出结论,叶酸 - 聚(酯胺)(FA - PEA)聚合物可用于靶向基因递送,并且基于可生物降解叶酸 - 聚(酯胺)聚合物和热敏PECE水凝胶的新型基因递送复合材料显示出持续基因释放的潜力。