Zhai Yinglei, Zhou Xing, Zhang Zhiqiang, Zhang Lei, Wang Dianyu, Wang Xinhui, Sun Wei
Department of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China.
Hainan Institute of Materia Medica, Haikou 570311, China.
Polymers (Basel). 2018 Oct 11;10(10):1127. doi: 10.3390/polym10101127.
The side effects of doxorubicin (DOX) extremely limit its application in the treatment of malignant tumors. Nano-sized polymeric drugs based on the acidic microenvironment of tissular- or intra- tumor have attracted ample attention because of their potential in reducing side effects. In this research, an amphiphilic diblock copolymer based on poly (ethylene glycol) (PEG) and functionalized polycaprolactone (PCL) was synthesized and utilized as the drug carrier. DOX was chemically conjugated with the polymer via acid-cleavable imine bonds to obtain a novel pH-sensitive DOX prodrug (mPEG-PCL-Imi-DOX). mPEG-PCL-Imi-DOX (24.2 wt % DOX content) formed micelles with an average diameter of 125 nm through a simple solvent evaporation method. The in vitro release profile demonstrated that DOX release of the prodrug micelles was pH-responsive and able to be accelerated with the decrease of pH. In vitro cytotoxicity assay tests revealed that the pH-sensitive DOX prodrug micelles exhibited relatively lower toxicity and similar antitumor efficacy towards MCF-7 cells compared with free DOX. Hence, the DOX prodrug micelles with imine bonds can offer a carrier with great potential for chemo-therapeutics.
阿霉素（DOX）的副作用极大地限制了其在恶性肿瘤治疗中的应用。基于组织或肿瘤内酸性微环境的纳米级聚合物药物因其在减少副作用方面的潜力而备受关注。在本研究中，合成了一种基于聚乙二醇（PEG）和功能化聚己内酯（PCL）的两亲性二嵌段共聚物，并将其用作药物载体。DOX通过酸可裂解的亚胺键与聚合物化学偶联，得到一种新型的pH敏感型DOX前药（mPEG-PCL-Imi-DOX）。mPEG-PCL-Imi-DOX（DOX含量为24.2 wt%）通过简单的溶剂蒸发法形成了平均直径为125 nm的胶束。体外释放曲线表明，前药胶束的DOX释放具有pH响应性，并且能够随着pH值的降低而加速。体外细胞毒性试验表明，与游离DOX相比，pH敏感型DOX前药胶束对MCF-7细胞表现出相对较低的毒性和相似的抗肿瘤疗效。因此，具有亚胺键的DOX前药胶束可为化疗药物提供具有巨大潜力的载体。
