中国药科大学学报2025,Vol.56Issue(6):729-736,8.DOI:10.11665/j.issn.1000-5048.2025060701
还原响应型纳米粒通过双重机制逆转非小细胞肺癌多药耐药性的研究
Redox-responsive nanoparticles reversing non-small cell lung cancer multidrug resistance via dual mechanisms
摘要
Abstract
A redox-responsive hyaluronic acid-vitamin E polyethylene glycol succinate nanoparticle loaded with paclitaxel(HA-SS-TPGS@PTX)was designed to investigate its mechanism for overcoming multidrug resistance(MDR)in non-small cell lung cancer(NSCLC)in vitro.HA-SS-TPGS@PTX nanoparticles were prepared using an emulsion-ultrasonication method.Techniques such as flow cytometry and confocal laser scanning microscopy(CLSM)were employed to study their effects on apoptosis induction,mitochondrial function,and the regulation of P-glycoprotein(P-gp)expression in PTX-resistant lung cancer cells(A549/T).Results showed that HA-SS-TPGS@PTX nanoparticles significantly inhibited the proliferation of A549/T cells in vitro,with an IC50 of 1.35 μg/mL.The nanoparticles entered the cells via CD44 receptor-mediated endocytosis.The high intracellular concentration of glutathione(GSH)triggered the release of PTX and TPGS,which subsequently induced a decrease in mitochondrial membrane potential,leading to apoptosis.Meanwhile,HA-SS-TPGS@PTX also inhibited P-gp expression and ATP consumption,thereby blocking drug efflux.The design of HA-SS-TPGS@PTX provides a new strategy for overcoming MDR in NSCLC.关键词
还原响应型纳米粒/多药耐药性/紫杉醇/非小细胞肺癌Key words
redox-responsive nanoparticles/multidrug resistance/paclitaxel/non-small cell lung cancer分类
医药卫生引用本文复制引用
朱峰,傅超婷,王亚洲,匡正,尹莉芳..还原响应型纳米粒通过双重机制逆转非小细胞肺癌多药耐药性的研究[J].中国药科大学学报,2025,56(6):729-736,8.基金项目
国家自然科学基金项目(No.82473864) This study was supported by the National Natural Science Foundation of China(No.82473864) (No.82473864)