CuO dot-decorated Cu@GdO core-shell hierarchical structure for Cu() self-supplying chemodynamic therapy in combination with MRI-guided photothermal synergistic therapy

Theoretically, the Fenton catalytic efficiency of the Cu-based nanoplatform is approximately 160 times that of traditional Fe-based agents. However, the coordination interaction between Cu( ii ) and intracellular GSH significantly inhibits the high catalytic activity of Cu( i ) generation, dramatically decreasing the Fenton-like catalytic efficiency. Herein, we designed a completely new and highly efficient hierarchical structural nanoplatform to enhance the mimic-peroxidase activity through utilizing comproportionation between CuO and elemental Cu core to self-supply Cu( i ). The catalytic rate of this nanoplatform was approximately 55-fold that of traditional Fe-based agents. In a cell assay, this nanoplatform could function as an antagonist of GPX4 and agonist of SOD-1, resulting in intracellular ROS and H 2 O 2 accumulation. Next, the accumulated H 2 O 2 could be quickly catalyzed to highly toxic &z.rad;OH by self-supplying Cu( i ), causing strong oxidative stress damage to mitochondria and cell membranes. Under 808 nm laser irradiation, this nanoplatform exhibited a stronger inhibition of tumor growth, and effectively overcame the tumor resistance and recurrence. In addition, this hierarchical structure significantly promoted the interaction between water molecules and gadolinium centers, making TRF-mCuGd possess an ultrahigh T 1 MRI contrast performance, and hence, more pathological information of the tumor could be achieved. Overall, this work provides a promising pattern for the design and development of cancer theranostics. Cu( i ) self-supplying core-shell nanoplatform is developed with enhanced Fenton-type catalytic activity for accelerating chemodynamic therapy in combination with MRI-guided photothermal synergistic therapy.