Endogenous H₂S-Activable Liposomal Nanoplatform for Synergistic Colorectal Tumor Ablation at Mild Apparent Temperature

Photoinduced hyperthermia possesses great potential in photothermal therapy and thermal-responsive chemotherapy of tumors. However, traditional thermal-triggered drug release requires high temperature, which results in unpleasant activation of thermal-induced cellular self-protection. In this work, a Cu-complex modified and drug-loaded liposomal nanoplatform was constructed for endogenous H₂S-activated synergistic ablation of colorectal tumors. In response to H₂S, the incorporated Cu-complex contributed to the formation of semiconductor CuS on the surface of the as-designed liposomal nanoplatform, which led to local heating under near-infrared (NIR) laser irradiation to achieve simultaneous photothermal therapy and drug release. It is noteworthy that although the drug release occurred at a mild apparent temperature, it was actually triggered by the high eigen temperature on the surface of the liposomal nanoplatform. Therefore, efficient and synergistic photothermal and chemotherapy was achieved under mild apparent temperatures. This work provides insights into achieving selective and bioactivated photothermal therapy and therefore thermal-controlled drug release without using excessive hyperthermia.