Phased-Change Materials Based Immunomodulator for Cascade-Activatable Tumor-Specific Photoimmunotherapy

The development of activatable immunomodulators for cancer treatment in a controlled and effective manner has been extensively pursued. However, the creation of a spatiotemporally controllable and cascade-activatable tumor-specific photoimmunotherapy platform for precise immunotherapy remains a challenge. Herein, cascade-activatable tumor-specific immunomodulators (CAI) are reported for cancer photoimmunotherapy. Under 808 nm irradiation, the CAI not only mediates phototherapy effect to achieve tumor eradication and immunogenic cell death but also triggers in situ release of caged toll-like receptor 7/8 R848-QPA. Additionally, the intracellular NQO1 activates R848-QPA, leading to the cleavage of trimethyl lock and release of active R848 agonist, enhancing the antitumor immune response. Such a cascade-activatable nanoimmunomodulator can effectively inhibit bilateral tumor growth and enhances systemic immune activation, resulting in improved infiltration of cytotoxic T lymphocytes and helper T cell. Therefore, this modular-designed engineered paradigm provides a generic strategy for developing immunomodulators for precise cascade-activatable immunotherapy.