A cascade nanoplatform for intelligent response to tumor microenvironment and collaborative cancer therapy.

Disulfiram (DSF), a new potential anticancer drug, has been shown to exhibit anticancer activity dependent on the formation of CuET, the chelation product of DSF with Cu. However, the poor stability of DSF and insufficient physiological concentration of Cu hinder its practical application. To achieve the co-delivery of DSF and Cu while overcoming the inefficiency of single chemotherapy, in this study, a cascade nanoplatform, DSF/Ce6@ZIF-8@CuO, was constructed by encapsulating DSF and chlorin e6 (Ce6, a photosensitizer) in zeolite imidazole framework-8 (ZIF-8, a nanocarrier) and then loading CuO, which self-supplied HO/O, onto DSF/Ce6@ZIF-8. By triggering the response of DSF/Ce6@ZIF-8@CuO to the acidic tumor microenvironment, encapsulated DSF, Ce6 and CuO were released to achieve multimodal synergistic treatment with enhanced DSF chemotherapy and chemodynamic/photodynamic therapy (CDT/PDT). and animal studies indicated that the designed DSF/Ce6@ZIF-8@CuO has strong tumor-inhibitory effects and provides a promising paradigm for designing smart nanoplatforms.