Multidrug resistance (MDR) is a primary cause of failure in oncotherapy and interest is growing in the design of multi-stimuli responsive nano-carriers to synergistically deliver chemotherapeutic agents and P-gp inhibitors to reverse MDR. The hybrid micelles based on a Platinum (IV)-coordinate polymeric prodrugs and TPGS were developed to improve chemotherapy and reduce side effects. The pH/redox dual-sensitive polymers were synthesized by condensation polymerization using ortho ester monomer and diamminedichlorodisuccinatoplatinum (DSP). The hybrid micelles possessed uniform size (38 nm) and displayed good stability in various physiological conditions. In contrast, in vitro drug release profiles indicated that these micelles could be completely depolymerized under acidic and reducing environment, thereby more than 80 % cisplatin were released within 12 h at pH 5.0 plus 10 mM DTT. More importantly, a large amount of TPGS released simultaneously could effectively inhibit the function of drug efflux pumps, which significantly enhanced the cytotoxicity of cisplatin against A549/DDP cells. The growth inhibition rate of micelles on A549/DDP multicellular spheroids was 79.5 %, while that of free cisplatin was only 6.8 %. Therefore, these hybrid micelles are promising in overcoming tumor MDR and worth doing further research in vivo and extend to other therapeutic agents.

多药耐药性 (MDR) 是肿瘤治疗失败的主要原因，人们越来越关注设计多刺激响应纳米载体以协同递送化疗药物和 P-gp 抑制剂来逆转 MDR。开发了基于铂 (IV) 配位聚合物前药和 TPGS 的混合胶束，以改善化疗并减少副作用。pH/氧化还原双敏感聚合物是通过使用原酸酯单体和二氨基二氯二琥珀酸铂（DSP）缩聚合成的。混合胶束具有均匀的尺寸（38 nm），并在各种生理条件下表现出良好的稳定性。相比之下，体外药物释放曲线表明，这些胶束在酸性和还原性环境下可以完全解聚，因此在 pH 5.0 加 10 mM DTT 条件下，12 小时内释放了 80% 以上的顺铂。更重要的是，同时释放的大量TPGS可以有效抑制药物外排泵的功能，从而显着增强顺铂对A549/DDP细胞的细胞毒性。胶束对A549/DDP多细胞球体的生长抑制率为79.5%，而游离顺铂仅为6.8%。因此，这些混合胶束在克服肿瘤 MDR 方面很有前景，值得在体内进行进一步研究并扩展到其他治疗剂。