Bidirectionally HO-suppliable and antioxidant-consumable copper peroxide nanoparticles for photochemodynamic immunotherapy.

Reactive oxygen species (ROS)-based antitumor compounds show great promise in cancer treatments such as chemodynamic therapy (CDT) and photodynamic therapy (PDT), but are severely restricted by both endogenous antioxidants and hydrogen peroxide (HO). Here, we synthesize bidirectionally HO-suppliable and antioxidant-consumable copper peroxide (CuO) nanoparticles for CDT/PDT-synergized immunotherapy against aggressive triple-negative breast cancers (TNBCs). The CuO nanoparticles are established to afford pH-responsive decomposition into HO and Cu, followed by the reduction into Cu by glutathione and subsequent catalysis reaction of HO into highly reactive ·OH, thus yielding CDT-mediated cell injury. Meanwhile, the glutathione consumption from the nanoparticles attenuates their ROS scavenging to promote singlet oxygen generation of co-assembled indocyanine green upon light exposure, thereby amplifying PDT-based cell damage. Moreover, the dully enhanced CDT/PDT damages of the nanoparticles provoke potent immunogenic cell death that further synergizes with immune checkpoint inhibitor via relieving indoleamine 2,3-dioxygenase 1-mediated immunosuppression, thus amplifying immunotherapeutic efficacy against primary, distant and metastatic TNBCs. This work provides valuable insights into nanomedicines for synergistic cancer therapy.