脂筏
PLGA公司
药物输送
流出
阿霉素
化学
药品
细胞凋亡
癌细胞
辛伐他汀
细胞内
药理学
细胞
细胞生物学
癌症
生物化学
生物
体外
化疗
有机化学
遗传学
作者
Bin Du,Wanying Zhu,Lili Yu,Yuehua Wang,Min Zheng,Jiazhu Huang,Guopeng Shen,Jie Zhou,Hanchun Yao
标识
DOI:10.1016/j.nano.2020.102307
摘要
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 (TPGS2k) was successfully synthesized and used to modify poly (lactic-glycolic acid) nanoparticles co-loaded with doxorubicin (DOX) and simvastatin (SV) (SV/DOX@TPGS2k-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.
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