Radiofrequency-Activated Pyroptosis of Bi-Valent Gold Nanocluster for Cancer Immunotherapy

Pyroptosis is gasdermin-mediated programmed necrosis that exhibits promising potential application in cancer immunotherapy, and the main challenge lies in how to provoke specific pyroptosis of tumor cells. Here, biGC@PNA with a precisely stoichiometric ratio of Au(I) ion/Au(0) atom induced pyroptosis of tumor cells by its radiofrequency (RF)-heating effect. An in vitro/in vivo assay on 4T1 tumor cells indicates RF-activated pyroptosis of tumor cells elicits a robust ICD effect, enhancing the synergistic antitumor efficacy of biGC@PNA with decitabine, significantly suppressing tumor metastasis and relapse by provoking systemic antitumor immune responses. Utilizing RF-activated pyroptotic immune responses, biGC@PNA efficiently enhances the antitumor efficacy of αPD-1 immunotherapy under RF irradiation and provides a promising strategy for improving cancer immunotherapy by the noninvasive RF field with high clinical transformation potential.