Multifunctional ginsenoside Rg3-integrated liposomes for synergistic chemo-photothermal-immunotherapy against multidrug-resistant breast cancer

Abstract

To address multidrug resistance (MDR) in breast cancer, a multifunctional liposome (RID-LPs) was developed by replacing cholesterol with ginsenoside Rg3 and incorporating DSPE-PEG2000 for prolonged systemic circulation. This nanoplatform encapsulates indocyanine green (ICG) as a photothermal agent and cisplatin (DDP) for chemotherapy. Rg3 functions as a key component to enhance cellular uptake via glucose transporter 1 (GLUT1) targeting and increase intracellular drug accumulation by inhibiting P-glycoprotein (P-gp) efflux pumps. Under 808 nm laser irradiation, ICG generates photothermal effects to induce pyroptosis and the release of damage-associated molecular patterns (DAMPs), which significantly promotes dendritic cells (DCs) maturation and T-cell activation for potent immunotherapy. Additionally, Rg3 promotes Caspase-3 expression to drive cell apoptosis. By combining targeted delivery, efflux inhibition, and immune system activation, RID-LPs effectively overcome MDR and achieve a synergistic therapeutic effect. This integrated strategy demonstrates excellent biosafety and provides a promising approach for the comprehensive treatment of drug-resistant breast cancer.