NIR-II-activated photothermal therapy using gold nanotetrapods enhances antigen presentation and immune response in colorectal cancer

Second window near-infrared (NIR-II) light is preferred for photothermal therapy due to its deeper tissue penetration, reduced scattering, and improved imaging guidance compared to NIR (I) light. However, NIR-II–absorbing gold nanomaterials with low cytotoxicity, well-defined structural stability, controllable size, and excellent dispersibility have been rarely reported. Compared with nanospheres and nanorods, gold nanostars have lower cytotoxicity, lower oxidative stress damage, higher intracellular enrichment in tumor cells, and maintain their labeling activity after circulation in vivo. Here, we reported a well-defined and easily synthesized gold nanotetrapods (AuNTPs) material absorbing NIR (II). This material not only meets the requirements for localized tumor hyperthermia but also reprograms the tumor microenvironment by enhancing tumor cell antigen presentation, converting "cold" tumors into "hot" tumors. Additionally, AuNTPs-based photothermal therapy induced by NIR-II irradiation enhances the antitumor functions of dendritic cells, T cells, and NK cells in the systemic immune response, inducing a sustained antitumor immune effect. The tumor microenvironment modulation properties exhibited by these AuNTPs may provide new avenues for exploring precise, non-invasive optical modulation nano anti-cancer therapy platforms within the NIR (II) window.