Macrophage Membrane-Engineered Nanovesicles Co-Delivering Ruxolitinib and Carvedilol for Synergistic Therapy of Cisplatin-Resistant Lung Cancer

Lung cancer is the leading cause of cancer death worldwide, and nonsmall cell lung cancer is the most common type. Cisplatin-based chemotherapy is still the cornerstone therapy for many patients, but its efficacy is often limited by the emergence of drug resistance, which makes it crucial to find strategies to overcome drug resistance. In order to solve the problem of cisplatin resistance in lung cancer, this study developed a macrophage membrane-camouflaged biomimetic nanovesicle system for codelivery of carvedilol (a β-adrenergic receptor blocker) and ruxolitinib (a selective JAK1/2 inhibitor). This system is designed to enable effective tumor targeting and responsive drug release. The prepared nanovesicles were characterized and proved to effectively inhibit the JAK2/STAT3 pathway in vitro, thereby inhibiting the proliferation of cisplatin-resistant A549 cells. In in vivo experiments, the system achieved targeted enrichment in lung tumors, significantly inhibited tumor growth by blocking JAK2/STAT3 phosphorylation, and maintained good biosafety. This study provides a promising biomimetic strategy for overcoming chemotherapy resistance.