Near-Infrared Light-Triggered Thermoresponsive Pyroptosis System for Synergistic Tumor Immunotherapy

Pyroptosis, as an inflammatory cell death, has been widely applied in tumor therapy, but its systemic adverse reactions caused by nonspecific activation still seriously hinder its application. Herein, a near-infrared (NIR) light-triggered thermoresponsive pyroptosis strategy is designed for on-demand initiation of pyroptosis and synergistic tumor immunotherapy. Specifically, glucose oxidase (GOx) loaded and heat-sensitive material p(OEOMA-co-MEMA) (PCM) modified mesoporous Pt nanoparticles (abbreviated as PCMPt/GOx) are prepared as the mild-temperature triggered pyroptosis inducer. Pt nanoparticles can not only serve as nanozyme with catalase-like activity to promote GOx catalytic reaction, but also act as photothermal agent to achieve mild-temperature photothermal therapy (PTT) and thermoresponsive GOx release on-demand under the irradiation of NIR light, thereby activating and promoting pyroptosis. In vitro and in vivo experiments prove that NIR light-triggered thermoresponsive pyroptosis system exhibits excellent antitumor immunity activity as well as significantly inhibits tumor growth. The precise control of pyroptosis by NIR light as well as pyroptosis cooperated with mild-temperature PTT for synergistically attenuated tumor immunotherapy are reported for the first time. This work provides a new method to initiate pyroptosis on demand, which is of great significance for spatiotemporally controllable pyroptosis and immunotherapy. The near-infrared light-triggered thermosensitive pyroptosis system (PCMPt/GOx) is designed. Under 808 nm laser irradiation, PCMPt/GOx can achieve precise on-demand release of GOx and mild photothermal therapy (PTT), thereby causing intracellular inflammatory stress response and inducing pyroptosis. The occurrence of pyroptosis and the reversal of the immunosuppressive TME trigger the anti-tumor immune response for synergistic tumor immunotherapy.image