Lu Hung-Hsun, Huang Cheng-Hung, Shiue Ting-Yun, Wang Fu-Sheng, Chang Ko-Kai, Chen Yunching, Peng Chi-How
Department of Chemistry , Frontier Research Center on Fundamental and Applied Sciences of Matters , National Tsing Hua University , 101, Sec 2, Kuang-Fu Rd. , Hsinchu 30013 , Taiwan . Email:
Institute of Biomedical Engineering , Frontier Research Center on Fundamental and Applied Sciences of Matters , National Tsing Hua University , 101, Sec 2, Kuang-Fu Rd. , Hsinchu 30013 , Taiwan.
Chem Sci. 2018 Oct 4;10(1):284-292. doi: 10.1039/c8sc01494a. eCollection 2019 Jan 7.
Triblock copolymer of poly(ethylene glycol)--poly(2-dimethylaminoethyl methacrylate)--poly(pyrenylmethyl methacrylate) (PEG--PDMAEMA--PPy) has been developed for use as an ideal gene delivery system, which showed both high stability under physiological conditions and efficient gene release in a mimetic cancer environment. The siRNA release from this system without external stimulation was 16% in 1 h and then remained steady. However, the photo-triggered siRNA release was 78% within 1 h and was higher than 91% after 24 h. The remarkable contrast between the stability and release efficiency of these siRNA-condensed micelleplexes before and after photo-irradiation has been rationalized by the light- and pH-induced structural transitions of the triblock copolymer micelles. The negligible cytotoxicity, high cellular uptake efficiency, and remarkable knockdown efficiency shown in tests further revealed the promising potential of these triblock copolymer micelleplexes for use in stimuli-responsive gene therapy.
聚（乙二醇）-聚（甲基丙烯酸2-二甲基氨基乙酯）-聚（芘甲基丙烯酸甲酯）三嵌段共聚物（PEG-PDMAEMA-PPy）已被开发用作理想的基因递送系统，该系统在生理条件下显示出高稳定性，并且在模拟癌症环境中能高效释放基因。在没有外部刺激的情况下，该系统在1小时内的siRNA释放率为16%，然后保持稳定。然而，光触发的siRNA释放在1小时内为78%，24小时后高于91%。光照射前后这些siRNA凝聚胶束复合物的稳定性和释放效率之间的显著差异已通过三嵌段共聚物胶束的光和pH诱导的结构转变得到合理解释。测试中显示的可忽略的细胞毒性、高细胞摄取效率和显著的敲低效率进一步揭示了这些三嵌段共聚物胶束复合物在刺激响应基因治疗中的潜在应用前景。
