Song Jian, Xu Bingbing, Yao Hui, Lu Xiaofang, Tan Yang, Wang Bingyang, Wang Xing, Yang Zheng
Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, China.
Front Oncol. 2021 Mar 25;11:656717. doi: 10.3389/fonc.2021.656717. eCollection 2021.
Developing efficacious drug delivery systems for targeted cancer chemotherapy remains a major challenge. Here we demonstrated a kind of pH-responsive PEGylated doxorubicin (DOX) prodrug the effective esterification and Schiff base reactions, which could self-assemble into the biodegradable micelles in aqueous solutions. Owing to low pH values inside the tumor cells, these PEG-Schiff-DOX nanoparticles exhibited high drug loading ability and pH-responsive drug release behavior within the tumor cells or tissues upon changes in physical and chemical environments, but they displayed good stability at physiological conditions for a long period. CCK-8 assay showed that these PEGylated DOX prodrugs had a similar cytotoxicity to the MCF-7 tumor cells as the free DOX drug. Moreover, this kind of nanoparticle could also encapsulate small DOX drugs with high drug loading, sufficient drug release and enhanced therapeutic effects toward MCF-7 cells, which will be benefited for developing more drug carriers with desirable functions for clinical anticancer therapy.
开发用于靶向癌症化疗的有效药物递送系统仍然是一项重大挑战。在此，我们展示了一种通过有效的酯化和席夫碱反应制备的pH响应性聚乙二醇化阿霉素（DOX）前药，其可在水溶液中自组装成可生物降解的胶束。由于肿瘤细胞内的低pH值，这些聚乙二醇-席夫碱-DOX纳米颗粒在肿瘤细胞或组织中，在物理和化学环境变化时表现出高载药能力和pH响应性药物释放行为，但在生理条件下能长时间保持良好的稳定性。CCK-8实验表明，这些聚乙二醇化DOX前药对MCF-7肿瘤细胞的细胞毒性与游离DOX药物相似。此外，这种纳米颗粒还可以高载药量封装小剂量的DOX药物，实现充分的药物释放并增强对MCF-7细胞的治疗效果，这将有助于开发更多具有理想功能的药物载体用于临床抗癌治疗。
