Engineering of an endogenous hydrogen sulfide responsive smart agent for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon cancer

INTRODUCTION: Photothermal therapy can be synergistically combined with chemotherapy to improve the therapeutic effect for colon cancer. However, conventional therapeutic agents have side effects in normal tissues, limiting their application. OBJECTIVES: To reduce these side effects, a smart agent (Cur@HKUST-1@PVP) whose functionality is triggered by the high content of endogenous hydrogen sulfide in colon tumors was engineered for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon tumors. METHODS: After reacting with hydrogen sulfide, Cur@HKUST-1@PVP simultaneously generates CuS and releases curcumin. The generated CuS serves as an imaging agent for both photothermal therapy and photoacoustic imaging, while the released curcumin is used for chemotherapy. RESULTS: In vivo photoacoustic imaging experiments demonstrated that Cur@HKUST-1@PVP can be used for selectively imaging colon cancer tumors. In vivo experiments in mice for treatment suggested that the endogenous hydrogen sulfide-activated combination of photothermal therapy and chemotherapy has a better treatment effect that photothermal therapy or chemotherapy treatment alone. CONCLUSION: The endogenous hydrogen sulfide-activated Cur@HKUST-1@PVP agent developed herein shows great potential for the accurate diagnosis and effective treatment of colon cancer.