An Endogenous H₂S-Activated Nanoplatform for Triple Synergistic Therapy of Colorectal Cancer.

Abstract

Overproduced hydrogen sulfide (H₂S) is a highly potential target for precise colorectal cancer (CRC) therapy; herein, a novel 5-Fu/Cur-P@HMPB nanomedicine is developed by coencapsulation of the natural anticancer drug curcumin (Cur) and the clinical chemotherapeutic drug 5-fluorouracil (5-Fu) into hollow mesoporous Prussian blue (HMPB). HMPB with low Fenton-catalytic activity can react with endogenous H₂S and convert into high Fenton-catalytic Prussian white (PW), which can generate <i>in situ</i> a high level of ^•OH to activate chemodynamic therapy (CDT) and meanwhile trigger autophagy. Importantly, the autophagy can be amplified by Cur to induce autophagic cell death; moreover, Cur also acted as a specific chemosensitizer of the chemotherapy drug 5-Fu, achieving a good synergistic antitumor effect. Such a triple synergistic therapy based on a novel nanomedicine has been verified both <i>in vitro</i> and <i>in vivo</i> to have high efficacy in CRC treatment, showing promising potential in translational medicine.