Dual-Modal Therapeutic Nanoplatform: Harnessing Caspase-1/GSDMD Pyroptosis and Photothermal Effects for Tumor Treatment

Currently, most cancer treatment strategies focus on surgical resection of malignant tumors, complemented by physicochemical therapies such as radiotherapy and chemotherapy. However, these approaches are plagued by critical limitations, including suppression of normal cell growth and severe systemic toxicity-related side effects. In recent years, novel cancer therapeutic modalities, particularly photothermal therapy (PTT), have arisen potentially viable alternatives to tumor therapy, because of their minimal side effects, precise controllability, and superior selectivity. This research is designed to develop an integrated antitumor, NIR-II-responsive nanoparticle, and to investigate its therapeutic potential through efficacy assessment in both cellular and animal models, along with mechanistic studies. Specifically, we engineered a hybrid nanosystem by incorporating the NIR-II fluorescent dye IR817 into the zeolitic imidazolate framework ZIF-8. This design strategy significantly enhances the IR817 photothermal conversion efficiency and bolsters the overall photothermal therapeutic efficacy. Notably, the dual functionality of ZIF-8 as both a nanocarrier and a pyroptosis inducer, combined with the photothermal effect of IR817, thereby provides improved overall antitumor outcomes.