College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, PR China.
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha, 410082, PR China.
Colloids Surf B Biointerfaces. 2020 Nov;195:111276. doi: 10.1016/j.colsurfb.2020.111276. Epub 2020 Jul 25.
Herein, we prepared novel reactive oxygen species (ROS) responsive core crosslinked (CCL/TK) polycarbonate micelles conveniently by click reaction between amphiphilic diblock copolymer poly(ethylene glycol)-poly(5-methyl-5-propargylxycar-bonyl-1,3-dioxane-2-one) (PEG-PMPC) with pendant alkynyl group and thioketal containing azide derivative bis (2-azidoethyl) 3, 3'- (propane-2, 2-diylbis (sulfanediyl)) dipropanoate (TK-N). The CCL/TK micelles were obtained with small size of 146.4 nm, showing excellent stability against dilution and high doxorubicin (DOX) loading. In vitro toxicity tests demonstrated that the obtained CCL/TK micelles have good biocompatibility and low toxicity with cell viability above 95 %. Furthermore, DOX-loaded CCL/TK micelles showed significantly superior toxicity with IC values for HeLa and MCF-7 cells about 3.74 μg/mL and 3.91 μg/mL, respectively. Confocal laser scanning microscope (CLSM) and flow cytometry showed excellent internalization efficiency and intracellular drug release of DOX-loaded CCL/TK micelles. The obtained ROS-responsive CCL/TK micelles showed great potential for anticancer drug delivery.
在此，我们通过具有侧基炔基的两亲性嵌段共聚物聚（乙二醇）-聚（5-甲基-5-炔丙基氧羰基-1,3-二氧戊环-2-酮）（PEG-PMPC）与含硫缩酮的叠氮衍生物双（2-叠氮乙基）3,3' -（丙烷-2,2-二基双（磺酰二基））二丙酸盐（TK-N）之间的点击反应，方便地制备了新型的活性氧（ROS）响应的核交联（CCL/TK）聚碳酸酯胶束。CCL/TK 胶束的粒径为 146.4nm，具有较小的粒径，表现出优异的稳定性，对稀释和高阿霉素（DOX）负载具有良好的稳定性。体外毒性试验表明，所得 CCL/TK 胶束具有良好的生物相容性和低毒性，细胞活力高于 95%。此外，载 DOX 的 CCL/TK 胶束对 HeLa 和 MCF-7 细胞的毒性显著提高，IC 值分别约为 3.74μg/mL 和 3.91μg/mL。共聚焦激光扫描显微镜（CLSM）和流式细胞术显示了载 DOX 的 CCL/TK 胶束优异的内化效率和细胞内药物释放。所得到的 ROS 响应性 CCL/TK 胶束在抗癌药物输送方面具有很大的潜力。
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