NIR-II-Responsive Carbon Dot/Bi₂S₃ Enables Mild Hyperthermia-Amplified Sonocatalytic Therapy Through Heterojunctions...

Sonodynamic therapy (SDT) demonstrates significant promise for noninvasive therapy of deep solid tumors such as cervical cancer, but its therapeutic efficacy is greatly restricted by low-efficiency sonosensitizers and the immunosuppressive tumor microenvironment (TME). Herein, we report the development of a novel Type-II carbon dot (CD)/Bi₂S₃ heterojunction for the mild NIR-II photothermal therapy (mPTT) amplified SDT/nanocatalytic therapy (NCT). The formation of heterojunctions drives the spatial separation of electron-hole pairs under ultrasound excitation, amplifying the generation of reactive oxygen species (ROS) while simultaneously utilizing highly oxidized holes to consume overexpressed GSH. In addition, under 1064 nm laser irradiation, the mild NIR-II photothermal effect generated by CD/Bi₂S₃ heterojunctions acts as a powerful thermodynamic accelerator, which not only enhances the intrinsic peroxidase (POD) and catalase (CAT) activities, but also relieves hypoxic TME. Based on the cascade amplification of ROS generation and reversal of immunosuppressive TME, CD/Bi₂S₃ heterojunctions not only achieve high-efficiency tumor eradication but also facilitate the infiltration of T cells in combination with PD-L1 inhibitors, successfully triggering a strong systemic antitumor immune response and inducing persistent immune memory. This work presents an innovative strategy for designing efficient heterojunction nanoplatforms that integrate mild NIR-II PTT, SDT, NCT, and TME regulation functions.