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

Abstract

The Cu²⁺ complex formed by the coordination of disulfiram (DSF) metabolite diethyldithiocarbamate (DTC), Cu(DTC)₂, can effectively inhibit tumor growth. However, insufficient Cu²⁺ levels in the tumor microenvironment can impact tumor-suppressive effects of DTC. In this study, we proposed a Cu²⁺ 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 Cu²⁺ on the outer layer. In the slightly acidic tumor microenvironment, TA/Cu undergoes hydrolysis, releasing Cu²⁺ and DSF, which further form Cu(DTC)₂ to inhibit tumor growth. Additionally, Cu²⁺ can engage in a Fenton-like reaction with H₂O₂ in the tumor microenvironment to form OH, therefore, chemodynamic therapy (CDT) and Cu(DTC)₂ 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.

Keywords: Chemodynamic therapy; Copper(Ⅱ)/diethyldithiocarbamate complex; Hollow mesoporous silica; Tannic acid/copper(Ⅱ) network; pH-responsive release.