Silencing the Catalase Gene with SiRNA for Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) has been emerging as a promising strategy for cancer treatment. But the CDT efficiency is restricted by the insufficient intracellular hydrogen peroxide (HO) level. Herein, we present a method for HO accumulation in tumor cells by silencing the catalase (CAT) gene with siRNA to achieve enhanced CDT. Cu-siRNA nanocomposites are fabricated by self-assembly of Cu and CAT siRNA and then modified with hyaluronic acid (HA) for active tumor targeting. After tumor cell uptake, the released Cu is reduced by highly expressed glutathione (GSH) to Cu, which then catalyzes HO to produce toxic hydroxyl radicals (OH) to kill tumor cells. CAT siRNA can efficiently silence the CAT mRNA to inhibit the consumption of HO, resulting in HO accumulation. The Cu-mediated GSH elimination and siRNA-induced endogenous HO enrichment both potentiate CDT. Cu-siRNA@HA exhibits good biocompatibility and therapeutic efficiency. This work thus paves a new way to supply HO in CDT and may hold potential for clinical application.