Biodegradable Persistent Luminescence Nanoparticles as Pyroptosis Inducer for High‐Efficiency Tumor Immunotherapy

Abstract Pyroptosis possesses potent antitumor immune activity, making pyroptosis inducer development a promising direction for tumor immunotherapy. Persistent luminescence nanoparticles (PLNPs) are highly sensitive optical probes extensively employed in tumor diagnosis and therapy. However, a pyroptosis inducer based on PLNPs has not been reported yet. Herein, polyethylene glycol–poly lactic acid‐co‐glycolic acid (PEG–PLGA: PP) modified biodegradable CaS:Eu 2+ (CSE@PP) PLNPs are synthesized as a pyroptosis inducer for tumor immunotherapy for the first time. The synthesized CSE@PP possesses biowindow persistent luminescence (PersL) and pH‐responsive degradation properties, allowing it to remain stable under neutral pH but degrade when exposed to weak acid (pH < 6.5). During degradation within the tumor, CSE@PP constantly releases H 2 S and Ca 2+ while its PersL gradually fades away. Thus, the PersL signal can self‐monitor H 2 S and Ca 2+ release. Furthermore, the released H 2 S and Ca 2+ result in mitochondrial dysfunction and the inactivation of reactive oxygen species scavenging enzymes, synergistic facilitating intracellular oxidative stress, which induces caspase‐1/GSDM‐D dependent pyroptosis and subsequent antitumor immune responses. In a word, it is confirmed that CSE@PP can self‐monitor H 2 S and Ca 2+ release and pyroptosis‐mediated tumor Immunotherapy. This work will facilitate biomedical applications of PLNPs and inspire pyroptosis‐induced tumor immunotherapy.