多西他赛与紫草素靶向共递送通过氧化启动增强非小细胞肺癌的放化疗效果

Abstract

Docetaxel (DTX)-based concurrent chemoradiotherapy (CCRT) is an important treatment for locally advanced non-small cell lung cancer (NSCLC), but its efficacy is limited by systemic toxicity and radioresistance. Here, we propose an oxidative priming strategy using plumbagin (PLB), a natural redox modulator, to disrupt tumor redox homeostasis and enhance DTX-mediated chemoradiotherapy. PLB markedly sensitized NSCLC cells to DTX, reducing the effective DTX concentration by 33.3-fold in LLC cells and 18-fold in A549 cells. To overcome the pharmacokinetic mismatch between DTX and PLB, we developed a folate receptor-targeted PEGylated liposomal nanoformulation for synchronized co-delivery. This formulation amplified intracellular ROS accumulation to approximately 2.5 times that induced by X-ray alone and 3.3 times that induced by (DTX + PLB)-NP alone, thereby enhancing radiation-induced DNA damage and apoptosis. In vivo, X-ray combined with the targeted nanoformulation achieved a tumor inhibition rate of 99%, while maintaining stable body weight and showing no obvious hematological, hepatic, or renal toxicity. This study provides a redox-guided nanomedicine strategy to enhance DTX-based CCRT for NSCLC at low doses while maintaining favorable preliminary biosafety.