Photoacoustic‐Imaging‐Guided Photothermal Regulation of Calcium Influx for Enhanced Immunogenic Cell Death
Mengxin Wang, Fengfeng Xue, Lu An, Dan Wu, Shuang Sha, Gang Huang, Qiwei Tian
Abstract
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.