Wang Jixue, Xu Weiguo, Ding Jianxun, Lu Shengfan, Wang Xiaoqing, Wang Chunxi, Chen Xuesi
Department of Urology, the First Hospital of Jilin University, Changchun 130021, China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Materials (Basel). 2015 Jan 12;8(1):216-230. doi: 10.3390/ma8010216.
Nanoscale micelles as an effective drug delivery system have attracted increasing interest in malignancy therapy. The present study reported the construction of the cholesterol-enhanced doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (CDM/DOX), poly(L-lactide)-based micelle (CLM/DOX), and stereocomplex micelle (CSCM/DOX) from the equimolar enantiomeric 4-armed poly(ethylene glycol)-polylactide copolymers in aqueous condition. Compared with CDM/DOX and CLM/DOX, CSCM/DOX showed the smallest hydrodynamic size of 96 ± 4.8 nm and the slowest DOX release. The DOX-loaded micelles exhibited a weaker DOX fluorescence inside mouse renal carcinoma cells (, RenCa cells) compared to free DOX·HCl, probably because of a slower DOX release. More importantly, all the DOX-loaded micelles, especially CSCM/DOX, exhibited the excellent antiproliferative efficacy that was equal to or even better than free DOX·HCl toward RenCa cells attributed to their successful internalization. Furthermore, all of the DOX-loaded micelles exhibited the satisfactory hemocompatibility compared to free DOX·HCl, indicating the great potential for systemic chemotherapy through intravenous injection.
纳米级胶束作为一种有效的药物递送系统，在恶性肿瘤治疗中引起了越来越多的关注。本研究报道了在水性条件下，由等摩尔对映体四臂聚（乙二醇）-聚丙交酯共聚物构建胆固醇增强的载阿霉素（DOX）聚（D-丙交酯）基胶束（CDM/DOX）、聚（L-丙交酯）基胶束（CLM/DOX）和立体复合胶束（CSCM/DOX）。与CDM/DOX和CLM/DOX相比，CSCM/DOX的流体动力学尺寸最小，为96±4.8nm，阿霉素释放最慢。与游离盐酸阿霉素相比，载阿霉素胶束在小鼠肾癌细胞（RenCa细胞）内的阿霉素荧光较弱，这可能是由于阿霉素释放较慢。更重要的是，所有载阿霉素胶束，尤其是CSCM/DOX，对RenCa细胞表现出与游离盐酸阿霉素相当甚至更好的优异抗增殖效果，这归因于它们成功内化。此外，与游离盐酸阿霉素相比，所有载阿霉素胶束均表现出令人满意的血液相容性，表明通过静脉注射进行全身化疗具有巨大潜力。
