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 CuO₂content critically compromises therapeutic efficacy. Here, tumor microenvironment (TME)-responsive RCD-CuO₂nanohybrids were designed by the in situ formation of CuO₂in the presence of red-emissive carbon dots (RCDs) as multifunctional stabilizers. The optimized RCD-CuO₂nanohybrids exhibited a high Cu content of 40.3% and a mean hydrodynamic diameter (D_h) of 153 nm. The proposed nanomedicine could disintegrate in the TME, releasing RCDs and CuO₂for 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 IC₅₀of 6.82 × 10³μg/mL for L02 cells, highlighting its promising potential for future tumor treatment.