Tumor cell membrane-coated acid-responsive CaCO3/MnCO nanoplatform for Ca2+ overload-amplified immunogenic cell death and STING-mediated cancer immunotherapy

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This study develops a hepatocellular carcinoma cell membrane-camouflaged hollow CaCO 3 -based nanoplatform for microenvironment-responsive gas-photothermal-immunotherapy. The biomimetic coating endows the nanoparticles with active targeting and immune evasion capabilities. In the acidic tumor/endolysosomal microenvironment, CaCO 3 decomposition induces Ca 2+ release and calcium overload, while MnCO releases CO gas to disrupt mitochondrial respiratory chain and Mn 2+ to activate cGAS-STING pathway for immune microenvironment remodeling. The incorporated DiR dye generates controllable photothermal effect under 808 nm laser irradiation, potentiating calcium influx via TRPV1 channel activation. Mechanistic studies reveal that the spatiotemporally coupled Ca 2+ /CO/Mn 2+ /photothermal synergy significantly amplifies mitochondrial dysfunction and systemic antitumor immunity. This work establishes a novel multimodal therapeutic paradigm for precision hepatocellular carcinoma treatment.