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

Lin Liu,Junpeng Shi,Jinyuan Wang,Linping He,Yan Gao,Peng Lin,Yutong Han,Ping'an Ma,Jun Lin,Yun Zhang

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.