The combination of doxorubicin (Dox) and glycyrrhetinic acid (GA) has been widely explored for treating various cancers, while the heterogeneous distribution, uncontrolled release and acid tumor microenvironment often hinder their synergistic effects. Herein, we introduce an acid/glutathione (GSH)-dual responsive nano-prodrug (AS1411@Dox+GA/NPs) enabling precise co-delivery of Dox and GA for enhanced combination therapy. The GSH-activated Dox prodrug [Poly(lactic-co-glycolic acid)-disulfide-Dox, PLGA-ss-Dox], GA, and sulfur-terminated D-α-tocopherol polyethylene glycol succinate (TPGS-SH) are combined to form a nanoemulsion with sodium bicarbonate (NaHCO