Copper-bacteriochlorin Nanosheet as A Specific Pyroptosis Inducer for Robust Tumor Immunotherapy.

Pyroptosis has been increasingly considered as a new weathervane in cancer immune therapy. However, triggering specific pyroptotic tumor cell death while preserving normal cells still remains a major challenge. Herein, for the first time, we designed a bran-new pyroptosis inducer, copper-bacteriochlorin nanosheet (Cu-TBB). The synthesized Cu-TBB could be activated to an "on" state in tumor microenvironment with glutathione (GSH) overexpression, leading to the release of Cu and TBB, respectively. Intriguingly, the released Cu could drive cascade reactions to produce O and highly toxic ·OH in cells. Additionally, the released TBB could also generate O and O upon 750 nm laser irradiation. Encouragingly, the both Cu -driven cascade reactions and photodynamic therapy pathways resulted in potent pyroptosis along with dendritic cell maturation and T cell priming, thus simultaneously eliminating the primary tumors and inhibiting the distant tumor growth and metastases. Conclusively, the well-designed Cu-TBB nanosheet has been shown to trigger specifical pyroptosis in vitro and in vivo, leading to enhanced tumor immunogenicity and antitumor efficacy while minimizing systemic side effects. This article is protected by copyright. All rights reserved.