Copper-Bacteriochlorin Nanosheet as a Specific Pyroptosis Inducer for Robust Tumor Immunotherapy

作者：Zhang, Yunxiu; Jia, Qingyan^*; Li, Jian; Wang, Jian; Liang, Ke; Xue, Xiaokuang; Chen, Tiejin; Kong, Lin; Ren, Haohui; Liu, Weimin; Wang, Pengfei^*; Ge, Jiechao^*

来源：Advanced Materials, 2023, 35(44).

DOI：10.1002/adma.202305073

• Cu-bacteriochlorin
• immunogenicity pyroptosis
• reactive oxygen species
• tumor microenvironment

Pyroptosis is increasingly considered a new weathervane in cancer immune therapy. However, triggering specific pyroptotic tumor cell death while preserving normal cells still remains a major challenge. Herein, a brand-new pyroptosis inducer, copper-bacteriochlorin nanosheet (Cu-TBB), is designed. The synthesized Cu-TBB can be activated to an "on" state in the tumor microenvironment with glutathione (GSH) overexpression, leading to the release of Cu+ and TBB, respectively. Intriguingly, the released Cu+ can drive cascade reactions to produce O2-& BULL; and highly toxic & BULL;OH in cells. Additionally, the released TBB can also generate O2-& BULL; and 1O2 upon 750 nm laser irradiation. Encouragingly, both Cu+-driven cascade reactions and photodynamic therapy pathways result 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 is shown to trigger specific pyroptosis in vitro and in vivo, leading to enhanced tumor immunogenicity and antitumor efficacy while minimizing systemic side effects. @@@ Copper-bacteriochlorin nanosheets as a specific pyroptosis inducer exhibit the ability to induce both Cu+-driven cascade reactions and photodynamic therapy to produce potent reactive oxygen species, leading to pyroptosis of primary tumors while promoting dendritic cell maturation and T cell activation, thereby enhancing tumor immunogenicity for inhibiting the distant tumor growth and metastases with minimal systemic side effects.image

• 单位
  中国科学院; 西北工业大学; 中国科学院研究生院