Recently, studies showed that the drug-resistant cell membranes have formed high-density lipid rafts regions; traditional targeted drug delivery systems can hardly break through the hard shell and deliver drugs to drug-resistant cells. Here, α-tocopherol polyethylene glycol 2000 succinate (TPGS_2k) was successfully synthesized and used to modify poly (lactic-glycolic acid) nanoparticles co-loaded with doxorubicin (DOX) and simvastatin (SV) (SV/DOX@TPGS_2k-PLGA NPs). The purpose of this study is to explore the synergistic effect between SV consuming cholesterol in lipid rafts and directly down-regulating P-gp expression on the intracellular drugs retention. The research highlights these nanoparticles interrupted lipid rafts (cholesterol-rich domains, where P-gp is often located), which inhibited drug efflux by down-regulating P-gp, promoted the mitochondria apoptosis and made SW620/AD300 cells (DOX-resistant colon cancer cell line) re-sensitized to DOX. Therefore, the carrier can become a promising SV-based nano-delivery system with depleting cholesterol in lipid rafts to reverse drug resistance.

近期研究表明，耐药细胞膜已形成高密度脂筏区；传统的靶向给药系统很难突破硬壳，将药物输送到耐药细胞。在这里，α-生育酚聚乙二醇 2000 琥珀酸酯 (TPGS _2k ) 被成功合成并用于修饰多柔比星 (DOX) 和辛伐他汀 (SV) 共负载的聚 (乳酸-乙醇酸) 纳米粒子 (SV/DOX@TPGS _2k-PLGA NP）。本研究的目的是探讨SV消耗脂筏中的胆固醇与直接下调P-gp表达对细胞内药物保留的协同作用。该研究强调这些纳米粒子中断了脂筏（富含胆固醇的结构域，P-gp 经常位于该区域），通过下调 P-gp 抑制药物外流，促进线粒体凋亡，并使 SW620/AD300 细胞（抗 DOX 结肠癌细胞系）对 DOX 重新敏感。因此，该载体可以成为一种很有前途的基于SV的纳米递送系统，可以消耗脂筏中的胆固醇来逆转耐药性。