Dual-Coordinated atomically dispersed Pt nanozymes evoke efficient pyroptosis for cancer immunotherapy

Pyroptosis, a distinct form of inflammatory programmed cell death, has emerged as novel therapeutic targets for igniting the immune system. Transition metal single-atom nanozymes (TM-SAzymes) hold great promise in inducing pyroptosis for enhanced immunotherapy due to their excellent catalytic activity and maximum atom utilization. However, fundamental understanding towards TM-SAzymes-induced pyroptosis and its associated signaling pathways in immunotherapy remains elusive. Herein, we developed atomically dispersed platinum nanozymes (Pt-NS/HCS) with sulfur (S) and nitrogen (N) coordination to effectively induce pyroptosis for enhanced immunotherapy. The obtained Pt-NS/HCS exhibited impressive peroxidase (POD)-like activity with a specific activity of 102 Umg−1. In vitro results demonstrate that Pt-NS/HCS effectively triggers Gasdermin D (GSDMD) and Gasdermin E (GSDME)-mediated pyroptosis, further causing robust immunogenic cell death (ICD). In vivo results further verify synergistically enhanced therapeutic effect of Pt-NS/HCS with programmed death ligand 1 (PD-L1) immunotherapies. This work provides valuable insights for the development of efficient TM-SAzymes and advanced synergistic approaches in clinical colon cancer treatment.