Novel glutathione (GSH)-dependent micelles based on carboxymethyl chitosan (CMCS) were developed for triggered intracellular release of doxorubicin (DOX). DOX-33'-Dithiobis (N-hydroxysuccinimidyl propionate)-CMCS (DOX-DSP-CMCS) prodrugs were synthesized. DOX was attached to the amino group on CMCS via disulfide bonds and drug-loaded micelles were formed by self-assembly. The micelles formed core-shell structure with CMCS and DOX as the shell and core, respectively, in aqueous media. The structure of the prodrugs was confirmed by IR and proton nuclear magnetic resonance (1H NMR) spectroscopy. The drug-loading capacity determined by UV spectrophotometry was 4.96% and the critical micelle concentration of polymer prodrugs determined by pyrene fluorescence was 0.089 mg/mL. Micelles were spherical and the mean size of the nanoparticles was 174 nm, with a narrow polydispersity index of 0.106. Moreover, in vitro drug release experiments showed that the micelles were highly GSH-sensitive owing to the reductively degradable disulfide bonds. Cell counting kit (CCK-8) assays revealed that DOX-DSP-CMCS micelles exhibited effective cytotoxicity against HeLa cells. Moreover, confocal laser scanning microscopy (CLSM) demonstrated that DOX-DSP-CMCS micelles could efficiently deliver and release DOX in the cancer cells. In conclusion, the DOX-DSP-CMCS nanosystem is a promising drug delivery vehicle for cancer therapy.

中文翻译：

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基于羧甲基壳聚糖的谷胱甘肽依赖性胶束，用于递送阿霉素。

基于羧甲基壳聚糖（CMCS）的新型谷胱甘肽（GSH）依赖性胶束被开发用于触发阿霉素（DOX）的细胞内释放。合成了DOX-33'-二硫代双（丙酸N-羟基琥珀酰亚胺酯）-CMCS（DOX-DSP-CMCS）前药。DOX通过二硫键连接到CMCS的氨基上，并通过自组装形成载药胶束。胶束在水性介质中分别以CMCS和DOX作为壳和核形成核-壳结构。通过IR和质子核磁共振（1H NMR）光谱确认了前药的结构。通过紫外分光光度法测定的载药量为4.96％，通过pyr荧光测定的聚合物前药的临界胶束浓度为0.089 mg / mL。胶束是球形的，纳米颗粒的平均尺寸为174 nm，的窄分散指数为0.106。此外，体外药物释放实验表明，由于可还原降解的二硫键，该胶束对GSH高度敏感。细胞计数试剂盒（CCK-8）分析表明，DOX-DSP-CMCS胶束对HeLa细胞表现出有效的细胞毒性。此外，共聚焦激光扫描显微镜（CLSM）证明DOX-DSP-CMCS胶束可以在癌细胞中有效地释放和释放DOX。总之，DOX-DSP-CMCS纳米系统是用于癌症治疗的有前途的药物输送工具。细胞计数试剂盒（CCK-8）分析表明，DOX-DSP-CMCS胶束对HeLa细胞表现出有效的细胞毒性。此外，共聚焦激光扫描显微镜（CLSM）证明DOX-DSP-CMCS胶束可以在癌细胞中有效地释放和释放DOX。总之，DOX-DSP-CMCS纳米系统是用于癌症治疗的有前途的药物输送工具。细胞计数试剂盒（CCK-8）分析表明，DOX-DSP-CMCS胶束对HeLa细胞表现出有效的细胞毒性。此外，共聚焦激光扫描显微镜（CLSM）证明DOX-DSP-CMCS胶束可以在癌细胞中有效地释放和释放DOX。总之，DOX-DSP-CMCS纳米系统是用于癌症治疗的有前途的药物输送工具。