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

• Published in: Advanced materials (Weinheim) 2023-11, Vol.35 (44), p.e2305073-n/a
• Main Authors: Zhang, Yunxiu, Jia, Qingyan, Li, Jian, Wang, Jian, Liang, Ke, Xue, Xiaokuang, Chen, Tiejin, Kong, Lin, Ren, Haohui, Liu, Weimin, Wang, Pengfei, Ge, Jiechao
• Format: Article
• Language: English
• Subjects: Anticancer properties; Biocompatibility; Cascade chemical reactions; Cell death; Copper; Cu‐bacteriochlorin; Glutathione; immunogenicity pyroptosis; Lymphocytes; Materials science; Nanosheets; Priming; reactive oxygen species; Side effects; tumor microenvironment
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202305073

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−• and highly toxic ·OH in cells. Additionally, the released TBB can also generate O2−• 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.