A Tumor Microenvironment-Responsive Theranostic Agent for Synergetic Therapy of Disulfiram-Based Chemotherapy and Chemodynamic Therapy

Despite the fact that chemotherapy has been widely used in the clinical treatment of breast cancer, the toxicity of chemotherapeutics to normal tissues cannot be ignored due to the low specificity. Therefore, due to the non-negligible toxicity of chemotherapeutic agents to normal tissues, tumor microenvironment (TME)-responsive cancer therapy has attracted a great deal of attention. Here, we report a TME-responsive theranostic nanoagent MnOx@PAA@HKUST-1-DSF@BSA fabricated via a layer-by-layer synthesis method. Once endocytosed by tumor cells, the nanoagent can be degraded into Mn²⁺ for magnetic resonance imaging and Cu²⁺ for Fenton-like reaction and chelating with released disulfiram in situ, achieving enhanced chemotherapy. Both in vitro and in vivo experiments demonstrate that the TME-targeted nanoagent can efficiently kill tumor cells. This work provides an alternative option for effective imaging and treatment of breast cancer without collateral damage to normal tissues.