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 Fe₃O₄ (CFO NPs) with large interaction interfaces, and electrons tend to transfer from Cu to Fe₃O₄ for the appearance of ≡Cu²⁺ and increase in ≡Fe²⁺. The generated ≡Cu²⁺ can interact with GSH, which prolongs the lifespan of ^•OH, produces ≡Cu⁺ for higher speed ^•OH generation with H₂O₂, and induces cell ferroptosis for tumor therapy. The improved ≡Fe²⁺ can also improve the ^•OH release under H₂O₂ until Cu is depleted. As a result, a sustainable ^•OH generation is achieved to promote cell apoptosis for effective tumor therapy. Since H₂O₂ 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.