Fe-Doped Carbon Dots-Incorporated In Situ Hydrogel for Near Infrared-Triggered Cascading Photothermal/Thermodynamic Therapy to Boost Cancer Immunity Cycle

Photothermal therapy-triggered whole-tumor cell antigens release has revolutionized in situ cancer vaccine, but insufficient anticancer immunity cycle activation greatly limits its curative effect. Herein, we designed an NIR-triggered cascading in situ vaccine (FCDs-A/C@HGs) by incorporating the Fe-doped carbon dots (FCDs), azo-initiator (AIPH), and immune adjuvant (cyclophosphamide) into the thermosensitive hydrogel. Due to iron doping, the as-prepared FCDs exhibited high photothermal conversion performance and favorable MR imaging capability. Upon intratumoral injection, local hyperthermia mediated by FCDs-A/C@HGs and the subsequent generation of alkyl radicals from AIPH synergistically induced immunogenic cell death in tumor cells. Remarkably, the FCDs-A/C@HGs elicited strong anticancer immune activation by inhibiting regulatory T cells and promoting dendritic cell maturation, thereby enhancing differentiation of cytotoxic CD8+ T cells and memory T cells. This study presents an effective therapeutic platform for in situ tumor suppression and sustained activation of the anticancer immunity cycle.