Self-assembled quercetin-Fe3+ nanoparticles for synergetic near-infrared light-triggered low-temperature photothermal/glutathione-activated chemodynamic therapy

Combining photothermal therapy (PTT) with chemodynamic therapy (CDT) is an efficacious strategy for cancer treatment. However, the hyperthermia-induced heat shock response and low Fenton reaction efficiency limited its clinical application. Here, we present self-assembled querce-tin-Fe3+ nanoparticles (Qu-Fe NPs) for synergetic near-infrared (NIR) light-triggered low-temperature PTT (LTPTT) and glutathione (GSH)-activated CDT. Qu-Fe NPs had a broad absorption range extending to the NIR region and excellent photothermal conversion ability. After endocytosis into cancer cells, these NPs partially released Qu that downregulated the expression of heat shock protein 70, in turn allowing for LTPTT. Moreover, Qu-Fe NPs could deplete the overexpressed GSH in cancer cells, increasing their sensitivity to reactive oxygen species. Meanwhile, Fe3+ could be reduced to Fe2+, which can react with endogenous H2O2 to generate hydroxyl radicals to achieve CDT. Heat generated by PTT could further accelerate the Fenton reaction in CDT, thus resulting in the synergistic effects between LTPTT and CDT. Both in vitro and in vivo results showed that Qu-Fe NPs could effectively inhibit tumor growth. This work presents a new approach for achieving mutually reinforced, synergetic NPs that can be used for LTPTT/CDT combination therapy.