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

Immunogenic cell death (ICD) induced by calcium ion (Ca2+) 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 Ca2+ by commonly used nanomodulators provides tumor cells with the opportunity to efficiently eliminate excess Ca2+ through ion channels, thus diminishing the therapeutic efficacy. Consequently, it is crucial to explore strategies for rapid Ca2+ release. To address this issue, a glutathione-triggered Ca(IO3)2@starch-based Ca2+ nanobomb is presented. This nanobomb not only enables accurate and efficient Ca2+ 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 Ca2+ influx. Both in vitro and in vivo results confirm that the photothermally regulated Ca2+ influx based on this Ca2+ nanobomb effectively promotes ICD and stimulates immune infiltration in tumor tissues, ultimately leading to the effective inhibition of tumor growth and metastasis. The developed Ca2+ nanobomb presents a potential strategy to enhance ICD based on Ca2+ overload, thus addressing the challenges associated with precise and timely regulation of Ca2+ influx and offering prospects for improved antitumor immunotherapy. An endogenous glutathione-triggered Ca(IO3)2@starch Ca2+ nanobomb is devised to investigated the impact of precise and efficient Ca2+ delivery on immunogenic cell death (ICD) resulting from Ca2+ overload. This innovative material integrates targeted Ca2+ delivery, swift Ca2+ release, and imaging-mediated regulation to optimize ICD induced by Ca2+ overload, thereby enhancing antitumor immunotherapy.image