In situ generation of copper(Ⅱ)/diethyldithiocarbamate complex through tannic acid/copper(Ⅱ) network coated hollow mesoporous silica for enhanced cancer chemodynamic therapy.

The Cu complex formed by the coordination of disulfiram (DSF) metabolite diethyldithiocarbamate (DTC), Cu(DTC), can effectively inhibit tumor growth. However, insufficient Cu levels in the tumor microenvironment can impact tumor-suppressive effects of DTC. In this study, we proposed a Cu and DSF tumor microenvironment-targeted delivery system. This system utilizes hollow mesoporous silica (HMSN) as a carrier, after loading with DSF, encases it using a complex of tannic acid (TA) and Cu on the outer layer. In the slightly acidic tumor microenvironment, TA/Cu undergoes hydrolysis, releasing Cu and DSF, which further form Cu(DTC) to inhibit tumor growth. Additionally, Cu can engage in a Fenton-like reaction with HO in the tumor microenvironment to form OH, therefore, chemodynamic therapy (CDT) and Cu(DTC) are used in combination for tumor therapy. In vivo tumor treatment results demonstrated that AHD@TA/Cu could accumulate at the tumor site, achieving a tumor inhibition rate of up to 77.6 %. This study offers a novel approach, circumventing the use of traditional chemotherapy drugs, and provides valuable insights into the development of in situ tumor drug therapies.