Cationic micelle-based siRNA delivery for efficient colon cancer gene therapy

被引:0
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作者
Yongping Lu
Lei Zhong
Zhongliang Jiang
Haixia Pan
Yuanfa Zhang
Guonian Zhu
Lan Bai
Rongsheng Tong
Jianyou Shi
Xingmei Duan
机构
[1] State Key Laboratory Breeding Base of Systematic research,Pharmacy College, Chengdu university of Traditional Chinese Medicine and The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicines of Ministry
[2] development and Utilization of Chinese Medicine Resources,Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine
[3] University of Electronic Science and Technology of China,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School
[4] Sylvester Comprehensive Cancer Center University of Miami,undefined
[5] Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital,undefined
[6] Sichuan University,undefined
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关键词
Non-viral vector; Gene therapy; Gene delivery; RNAi; siRNA; C26 colon cancer;
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学科分类号
摘要
Small interfering RNA (siRNA)-based gene therapy has provided an alternative strategy for cancer therapy. One of the key components within gene therapy process is the delivery system. As a novel non-viral gene vector, DMP, prepared by modifying mPEG-PCL micelle with cationic DOTAP lipid, has been prepared and successfully applied in plasmid DNA-based colon cancer gene therapy study. However, its potential in siRNA delivery is unknown. In this study, the preparation process of DMP was optimized and the anti-cancer efficacies of the DMP/siMcl1 and DMP/siBcl-xl complexes were studied on a mouse colon cancer model. Our results demonstrated that DMP cationic micelle-delivered siRNAs could effectively inhibit the growth of C26 colon cancer cells in vitro. Meanwhile, intratumoral administration of DMP/siMcl1 and DMP/siBcl-xl complexes obviously suppressed subcutaneous tumor model in vivo. These results suggest the DMP/siRNA complex to be a potential candidate for cancer gene therapy.
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