Rhythm Mild‐Temperature Photothermal Therapy Enhancing Immunogenic Cell Death Response in Oral Squamous Cell Carcinoma

Abstract The low antitumor efficiency and unexpected thermo‐tolerance activation of mild‐temperature photothermal therapy (mPTT) severely impede the therapeutic efficacy, thereby the implementation of reasonable mPTT procedure to improve antitumor efficiency is of great significance for clinical transformation. Herein, a rhythm mPTT with organic photothermal nanoparticles (PBDB‐T NPs) is demonstrated, synergistically increasing tumor elimination and intense immunogenic cancer cell death (ICD) to elicit tumor‐specific immune responses for tumor treatment. Specifically, PBDB‐T NPs are characterized by favorable biocompatibility, excellent and controllable photothermal properties, exhibit the properties of noninvasive diagnostic imaging, and effective mPTT against oral squamous cell carcinoma (OSCC). Encouragingly, a temperature‐dependent release of damage‐associated molecular patterns (DAMPs) is discovered during the mPTT‐induced ICD. Meanwhile, orchestrated rhythm mPTT referring to radiotherapy procedure amplifies and balances antitumor efficiency and abundant DAMPs generation to gain optimal immune activation within clinical‐recommended hyperthermia temperature compared with conventional PTT. The in vitro and in vivo results show that the rhythm mPTT unites the killing effect and ICD induction, generating strong mPTT efficacy and active tumor‐specific adaptive immune responses. The study offers a promising strategy and a new opportunity for the clinical application of mPTT.