Intraparticle Electron Transfer for Long-Lasting Tumor Chemodynamic Therapy.

Chemodynamic therapy (CDT) is a novel tumor treatment method by using hydroxyl radicals (OH) to kill cancer cells. However, its therapeutic effects are strictly confined by the short lifespan of OH and reduced OH generation speed. Herein, an effective CDT is achieved by both improving OH lifetime and long-lasting generating OH through intraparticle electron transfer within heterogeneous nanoparticles (NPs). These heterogeneous NPs are composed of evenly distributed Cu and FeO (CFO NPs) with large interaction interfaces, and electrons tend to transfer from Cu to FeO for the appearance of ≡Cu and increase in ≡Fe. The generated ≡Cu can interact with GSH, which prolongs the lifespan of OH, produces ≡Cu for higher speed OH generation with HO, and induces cell ferroptosis for tumor therapy. The improved ≡Fe can also improve the OH release under HO until Cu is depleted. As a result, a sustainable OH generation is achieved to promote cell apoptosis for effective tumor therapy. Since HO and GSH are only overexpressed at tumor, and CFO NPs can degrade in the tumor microenvironment, these NPs are with high biosafety and can be metabolized by urine. This work provides a novel biomaterial for effective cancer CDT through intraparticle electron transfer.