Duan Xiao, Bai Ting, Du Junjie, Kong Jie
MOE Key Laboratory of Space Applied Physics and Chemistry, Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
J Mater Chem B. 2018 Jan 7;6(1):39-43. doi: 10.1039/c7tb02817b. Epub 2017 Dec 8.
We present a novel glutathione-responsive amphiphilic drug self-delivery (DSD) micelle with one-pot synthesis to synergistically address the problems of controlled drug release, degradability, drug tracing and in vivo accumulated toxicity. The anticancer drug doxorubicin (DOX), disulfide-based diacrylate (DSDA) and amino-polyethylene glycol monomethyl ether were linked by Michael addition in one-pot synthesis. The accumulative release rate of DOX analogues with drug activity from the micelles was 67.9% under pH 7.4 and GSH = 1 mg mL conditions after 72 h. The cell uptake experiment showed that the micelles of DOX-DSDA-PEG were indeed taken up by A549 cells and distributed to cell nuclei. The in vitro cell viability of A549 cells was evaluated by CCK-8 and Muse Annexin V & Dead Cell Kit. The results illustrated that the completely biodegradable micelles with glutathione-responsive bonds in the backbone are an effective drug self-delivery system for tumor therapy in the future.
我们展示了一种通过一锅法合成的新型谷胱甘肽响应性两亲性药物自递送（DSD）胶束，以协同解决药物控释、可降解性、药物追踪和体内累积毒性等问题。抗癌药物阿霉素（DOX）、基于二硫化物的二丙烯酸酯（DSDA）和氨基聚乙二醇单甲醚通过迈克尔加成反应在一锅法合成中连接。在pH 7.4和谷胱甘肽=1 mg/mL条件下，72小时后，具有药物活性的DOX类似物从胶束中的累积释放率为67.9%。细胞摄取实验表明，DOX-DSDA-PEG胶束确实被A549细胞摄取并分布到细胞核中。通过CCK-8和Muse Annexin V与死细胞试剂盒评估A549细胞的体外细胞活力。结果表明，主链中具有谷胱甘肽响应键的完全可生物降解胶束是未来肿瘤治疗中一种有效的药物自递送系统。
