Redox-responsive nanoparticles reversing non-small cell lung cancer multidrug resistance via dual mechanisms
10.11665/j.issn.1000-5048.2025060701
- VernacularTitle: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
- Author:
Feng ZHU
1
;
Chaoting FU
;
Yazhou WANG
;
Zheng KUANG
;
Lifang YIN
Author Information
1. 海南通用三洋药业有限公司, 海口 570312;中国药科大学药学院药剂系, 南京 210009
- Publication Type:Journal Article 期刊文章
- Keywords:
redox-responsive nanoparticles;
multidrug resistance;
paclitaxel;
non-small cell lung cancer
- From:
Journal of China Pharmaceutical University
2025;56(6):729-736
- CountryChina
- Language:Chinese
-
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.
