Vitamin E d-ɑ-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) and indomethacin (IDM) can reverse multidrug resistance (MDR) via inhibiting P-glycoprotein (P-gp) and multidrug resistance associated protein 1 (MRP1) respectively, but their drawbacks in physicochemical properties limit their clinical application. To overcome these defects and enhance MDR reversal, the amphiphilic TPGS-IDM twin drug was successfully synthesized via esterification, and could self-assemble into free and paclitaxel-loaded (PTX-loaded) micelles. The micelles exhibited lower CMC values (5.2 × 10⁻⁵mg/mL), long-term stability in PBS (pH 7.4) for 7 days and SDS solution (5 mg/mL) for 3 days, and effective drug release at esterase/pH 5.0. Moreover, the micelles could down-regulate ATP levels and promote ROS production in MCF-7/ADR via the mitochondrial impairment, therefore achieving MDR reversal and cell apoptosis. Additionally, the PTX-loaded micelles could significantly inhibit the cell proliferation and promote apoptosis for MCF-7/ADR via the synergistic chemosensitizing effect of TPGS and IDM, and synergistic cytotoxic effect of TPGS and PTX. Thus, the chemosensitizing micelles self-assembled from amphiphilic TPGS-indomethacin twin drug have the great potentials for reversing MDR in clinical cancer therapy.

维生素E d-ɑ-生育酚聚（乙二醇）1000琥珀酸酯（TPGS）和吲哚美辛（IDM）可以通过分别抑制P-糖蛋白（P-gp）和多药耐药相关蛋白1（MRP1）来逆转多药耐药（MDR），但它们在理化性质上的缺点限制了它们的临床应用。为了克服这些缺陷并增强 MDR 逆转，通过酯化成功合成了两亲性 TPGS-IDM 双胞胎药物，并且可以自组装成游离和载有紫杉醇（PTX 载）的胶束。胶束表现出较低的 CMC 值 (5.2 × 10 ^-5mg/mL)，在 PBS (pH 7.4) 和 SDS 溶液 (5 mg/mL) 中长期稳定 7 天，在酯酶/pH 5.0 下有效释放药物。此外，胶束可通过线粒体损伤下调 ATP 水平并促进 MCF-7/ADR 中 ROS 的产生，从而实现 MDR 逆转和细胞凋亡。此外，载有 PTX 的胶束可通过 TPGS 和 IDM 的协同化学增敏作用以及 TPGS 和 PTX 的协同细胞毒作用显着抑制 MCF-7/ADR 的细胞增殖和促进细胞凋亡。因此，由两亲性TPGS-吲哚美辛双药自组装的化学增敏胶束在临床癌症治疗中具有逆转MDR的巨大潜力。