CuO dot-decorated Cu@Gd2O3 core–shell hierarchical structure for Cu(i) self-supplying chemodynamic therapy in combination with MRI-guided photothermal synergistic therapy

Abstract

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 H₂O₂ accumulation. Next, the accumulated H₂O₂ could be quickly catalyzed to highly toxic ˙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 T₁ 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.