Juglone-loaded metal-organic frameworks for H2O2 self-modulating enhancing chemodynamic therapy against prostate cancer

Abstract

As an innovative treatment strategy for cancer treatment, Fenton reaction-mediated Chemodynamic therapy (CDT) dependent on the conversion of endogenous hydrogen peroxide (H2O2) into cytotoxic hydroxyl radical (•OH) to destroy tumor cells has attracted increasing interest. However, the insufficient supply of H2O2 has greatly hindered the anticancer efficacy of CDT in the tumor microenvironment, and this inherent disadvantage has rarely attracted attention. In order to develop a strategy with high-efficiency H2O2 self-supply ability to enhance the CDT efficacy, we constructed a Fe-based metal–organic framework (MOF) as a carrier for the drug Juglone (JUG), which can not only increase the intracellular H2O2 concentration, but also serve as an inhibitor of the peptidyl-prolyl cis–trans isomerase NIMA-interacting 1 (Pin1), which is a key regulator for multiple physiological processes in cancer cells. Once internalized by tumor cells, the acidic environment of the tumor promotes the release of JUG for drug therapy, and the released Fe ions trigger the Fenton reaction to produce •OH from sufficient H2O2, thereby achieving significant antitumor effects. Furthermore, the coating of cancer cell membranes onto the JUG-loaded MOF could enable it with homologous tumor targeting ability. Both in vitro and in vivo results show that the use of drugs can activate the cascade to provide sufficient H2O2 with outstanding anti-tumor efficacy, which paves a new avenue for the realization of drug/CDT synergistic therapy.