Nano-Confined Radical Anion as An NIR-II Photothermal Immunogenic Amplifier for In Situ Cancer Vaccination.

Immunogenic cell death (ICD) induced by photothermal therapy holds promise for eliciting systemic antitumor immunity; however, its efficacy is frequently limited by tumor-intrinsic immunosuppressive defenses. Herein, we report a nano-confined radical anion as a photothermal immunogenic amplifier that exploits kinetic stabilization to couple high NIR-II photothermal efficiency with active glutathione depletion for robust in situ cancer vaccination. This amplifier is constructed through the simple co-assembly of terrylene diimide (TDI) with Pluronic F127, forming nanoparticles in which stable TDI radical anions are generated and kinetically stabilized. The radical anion nanoparticles are further integrated into an injectable hydrogel to create a multifunctional in situ vaccine. This platform ensures prolonged tumor retention, captures tumor-associated antigens released during ICD, and provides intrinsic adjuvanticity. In murine models, local laser activation of the platform ablates primary tumors and elicits systemic antitumor immune responses associated with suppression of distant tumor growth. The stabilization of organic radical anions by molecular and supramolecular design combines local photothermal therapy with systemic anti-tumor immunity.