Liposome-coated nanoparticle triggers prostate cancer ferroptosis through synergetic chemodynamic-gas therapy

Ferroptosis has attracted much attention for tumor treatment. It has been recently identified that castration-resistant prostate cancer (CRPC) is vulnerable to ferroptosis inducers. Notably, chemodynamic therapy (CDT), triggered by metal ions, could easily induce ferroptosis via a Fenton/Fenton-like reaction, but its efficiency was highly dependent on the intracellular H 2 O 2 concentration, posing significant changes for its clinical translation. Herein, we attached glucose oxidase (GOx) onto the surface of manganese sulfide (MnS) and developed therapeutic nanocomposites (Lpo@MnS-GOx) after encapsulating with liposome. Upon internalization by cancer cells, the released GOx could transform glucose into gluconic acid (GA) and H 2 O 2 . Notably, the generated GA stimulates the degradation of MnS, followed by the promotion of the release of H 2 S and Mn 2+ , whereas the produced H 2 O 2 can amplify the Fenton-like response initiated by Mn 2+ . The enhanced CDT combined with the gas therapy effect could simultaneously promote the accumulation of reactive oxygen species and finally induce ferroptosis and exhibit an excellent anti-tumor effect. Consequently, these Lpo@MnS-GOx NPs with enhanced ferroptosis-induced effect will find great potential for CRPC cancer treatment. Lpo@MnS-GOx induced prostate cancer ferroptosis through Chemodynamic-Gas therapy, which combined with starvation therapy exhibited co-enhanced anti-tumor effect.