Engineering 2D silicene-based core/shell nanomedicine for GSDME-induced synergistic pyroptosis and photonic hyperthermia of melanoma carcinoma

Pyroptosis has been recognized as an effective cancer-therapeutic modality, but how to efficiently trigger pyroptosis at the tumor region and improve the therapeutic efficiency remains highly challenging. In this work, a collaborative nanotherapeutic strategy is implemented in a two-dimensional (2D) silicene-based nanosystem, which simultaneously loads cisplatin (DDP) for inducing synergistic pyroptosis and photonic hyperthermal nanotherapy. 2D silicene nanosheet, as an excellent candidate of photothermal-conversion nanoagent and drug-delivery nanosystem, has been engineered by a mesoporous silica layer to enhance hydrophilicity, deliver drug on-demand, and supplement abundant chemical groups for targeting modification. Under near infrared laser irradiation, the engineered 2D core/shell nanosystem can rapidly generate heat shock and boost the DDP release for activating caspase-3 and cleaving silent GSDME into cytotoxic GSDME-N terminals, aiming to induce the synergistic pyroptosis and hyperthermia ablation for efficiently eliminating the melanoma carcinoma. This distinct photonic hyperthermia synergized with pyroptosis is instructive to the further design of therapeutic regimen against malignant carcinomas.