CuO₂-Based Nanohybrids for Tumor-Specific Fluorescence Imaging-Guided Double-Enhanced Chemodynamic Therapy

Copper peroxide (CuO2) nanoparticles have been proposed as promising nanotherapeutic candidates for self-enhanced chemodynamic therapy (CDT) through Fenton-like reactions. However, clinical application is still restricted by their ultrafine size and high activity. While the desired size and stability of the supported nanomedicine could be improved by using inert supports or excipients, the inevitable dilution of CuO2 content critically compromises therapeutic efficacy. Here, tumor microenvironment (TME)-responsive RCD-CuO2 nanohybrids were designed by the in situ formation of CuO2 in the presence of red-emissive carbon dots (RCDs) as multifunctional stabilizers. The optimized RCD-CuO2 nanohybrids exhibited a high Cu content of 40.3% and a mean hydrodynamic diameter (Dh) of 153 nm. The proposed nanomedicine could disintegrate in the TME, releasing RCDs and CuO2 for fluorescence imaging and photothermal (PT) effect and H2O2-self-supplying double-enhanced CDT. Benefiting from the TME-responsive synergetic enhancement of PT conversion and H2O2-self-supplying, a significantly lower half-maximal inhibitory concentration (IC50) of 13.81 μg/mL was achieved for HepG2 cells compared with an IC50 of 6.82 × 103 μg/mL for L02 cells, highlighting its promising potential for future tumor treatment.