谷胱甘肽触发的多柔比星和喜树碱双重释放用于高效协同抗癌治疗。
Glutathione-triggered dual release of doxorubicin and camptothecin for highly efficient synergistic anticancer therapy.
机构信息
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China; Department of Chemistry, Northeast Normal University, Changchun 130022, PR China.
出版信息
Colloids Surf B Biointerfaces. 2018 Sep 1;169:273-279. doi: 10.1016/j.colsurfb.2018.05.025. Epub 2018 May 17.
An amphiphilic biodegradable prodrug (PLG-g-mPEG/CPT) was synthesized by conjugating disulfide-containing camptothecin (CPT) to poly(L-glutamic acid)-graft-methoxy poly(ethylene glycol) (PLG-g-mPEG) through esterification reaction. The amphiphilic prodrugs could self-assemble into micellar nanoparticles and encapsulate doxorubicin (DOX) in aqueous solution at pH 7.4. The treatment of the nanoparticles with reducing glutathione (GSH) at cytosolic concentration (10 mM) significantly promoted the in vitro dual release of DOX and CPT from the micelles. The results of flow cytometry (FCM) and confocal laser scanning microscopy (CLSM) manifested that the intracellular release of DOX and CPT from the micelles was enhanced by increasing the intracellular GSH level. Consistently, the MCF-7 cell killing mediated by the micelles was also intracellular GSH concentration-dependent. The low combination index (CI) value of < 0.3 demonstrated the high synergistic effect of DOX and CPT co-delivered by the nanoparticles in tumor cell killing. Therefore, this GSH-triggered dual release drug delivery system is a promising strategy for combination cancer therapy.
一种两亲性可生物降解前药（PLG-g-mPEG/CPT）是通过酯化反应将含二硫键的喜树碱（CPT）连接到聚（L-谷氨酸）-接枝-甲氧基聚（乙二醇）（PLG-g-mPEG）上合成的。两亲性前药可以自组装成胶束纳米粒子，并在 pH 7.4 的水溶液中包载阿霉素（DOX）。用细胞内浓度（10mM）的还原型谷胱甘肽（GSH）处理纳米粒子，可显著促进 DOX 和 CPT 从胶束中的体外双重释放。流式细胞术（FCM）和共聚焦激光扫描显微镜（CLSM）的结果表明，通过增加细胞内 GSH 水平，从胶束中释放 DOX 和 CPT。一致地，由胶束介导的 MCF-7 细胞杀伤也依赖于细胞内 GSH 浓度。低组合指数（CI）值<0.3 表明纳米粒共递送 DOX 和 CPT 对肿瘤细胞杀伤具有很高的协同作用。因此，这种 GSH 触发的双重释放药物递送系统是联合癌症治疗的一种有前途的策略。
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