In vivo precise photothermal modulation to enhance cancer immunotherapy via NIR-II imaging-guided temperature feedback

Hyperthermia, as a promising immunoadjuvant strategy, primarily remodels the tumor microenvironment via immunogenic cell death (ICD) and immune cell recruitment, enabling novel combination immunotherapies. Nevertheless, the challenge of precisely regulating and maintaining temperature in vivo means that the thermal parameters required for optimal immune activation have yet to be fully elucidated. Herein, we propose a precise thermoregulation strategy guided by NIR-II imaging, which leverages temperature feedback based on AgAuSe quantum dot (QD) fluorescence and spatiotemporally encoded laser irradiation modulation to facilitate the investigation of thermally mediated immune activation in vivo. For this purpose, we developed a photothermal immuno-nanomedicine, namely ACF@QD, in which AF7P enables targeting of tumor cells; FS-mPEG serves as an efficient photothermal agent for thermal ablation; QD is used for temperature monitoring inside the tumor; and CpG enhances the antigen-presenting function of macrophages and dendritic cells (DCs). After accumulation of ACF@QD in the tumor, precise regulation of the local tumor temperature in vivo was achieved through temporally controlled combined laser irradiation guided by NIR-II fluorescence imaging. We revealed the in vivo temperature-dependent processes of ICD in tumor cells, as well as the recruitment and infiltration of immune cells, and validated the efficacy of 46 °C as an optimal temperature parameter in synergistically activating immune responses for breast cancer therapy.