Photoacoustic‐Imaging‐Guided Photothermal Regulation of Calcium Influx for Enhanced Immunogenic Cell Death

Abstract Immunogenic cell death (ICD) induced by calcium ion (Ca 2+ ) overload has attracted significant attention owing to its ability to activate the immune system and generate durable antitumor immune responses. However, the slow release of Ca 2+ by commonly used nanomodulators provides tumor cells with the opportunity to efficiently eliminate excess Ca 2+ through ion channels, thus diminishing the therapeutic efficacy. Consequently, it is crucial to explore strategies for rapid Ca 2+ release. To address this issue, a glutathione‐triggered Ca(IO 3 ) 2 @starch‐based Ca 2+ nanobomb is presented. This nanobomb not only enables accurate and efficient Ca 2+ delivery to the tumor site but also exploits glutathione‐triggered photoacoustic (PA) imaging‐guided photothermal precise control of TRPV1 ion channel activation for enhancing the Ca 2+ influx. Both in vitro and in vivo results confirm that the photothermally regulated Ca 2+ influx based on this Ca 2+ nanobomb effectively promotes ICD and stimulates immune infiltration in tumor tissues, ultimately leading to the effective inhibition of tumor growth and metastasis. The developed Ca 2+ nanobomb presents a potential strategy to enhance ICD based on Ca 2+ overload, thus addressing the challenges associated with precise and timely regulation of Ca 2+ influx and offering prospects for improved antitumor immunotherapy.