Tumor Microenvironment-Responsive Reagent DFS@HKUST-1 for Photoacoustic Imaging-Guided Multimethod Therapy

Although multimethod therapy has shown great promise for effective cancer treatment, it is still a great challenge to develop simple and effective strategies to construct multifunctional therapeutic reagents. According to the characteristics of the tumor microenvironment, such as a mild acidic environment and overexpression of H₂O₂, an intelligent therapeutic reagent with photoacoustic (PA) imaging-guided photothermal therapy, chemodynamic therapy, and in situ chemotherapy was constructed by simply loading disulfiram (DSF) in a Cu-based porous metal-organic framework (HKUST-1). The resultant material DFS@HKUST-1 shows near-infrared adsorption around 600-900 nm and effective photoacoustic imaging properties and photothermal conversion efficiency upon 808 nm irradiation. Besides, after DFS@HKUST-1 is enriched in the tumor, the acidic environment of the tumor will slowly trigger the decomposition of HKUST-1, leading to the release of Cu²⁺ ions to react with DSF and endogenous H₂O₂ to generate the Cu/DSF complex (CuET) and cytotoxic •OH for chemotherapy and chemodynamic therapy, respectively. Therefore, DFS@HKUST-1 can serve as a promising tumor microenvironment response therapeutic reagent for photoacoustic imaging-guided multimethod therapy.