Copper(II) Oxide Spindle-like Nanomotors Decorated with Calcium Peroxide Nanoshell as a New Nanozyme with Photothermal and Chemodynamic Functions Providing ROS Self-Amplification, Glutathione Depletion, and Cu(I)/Cu(II) Recycling

Uniform, mesoporous copper(II) oxide nanospindles (CuO NSs) were synthesized via a method based on templated hydrothermal oxidation of copper in the presence of monodisperse poly(glycerol dimethacrylate-co-methacrylic acid) nanoparticles (poly(GDMA-co-MAA) NPs). Subsequent decoration of CuO NSs with a CaO2 nanoshell (CuO@CaO2 NSs) yielded a nanozyme capable of Cu(I)/Cu(II) redox cycling. Activation of the Cu(I)/Cu(II) cycle by exogenously generated H2O2 from the CaO2 nanoshell significantly enhanced glutathione (GSH) depletion. CuO@CaO2 NSs exhibited a 2-fold higher GSH depletion rate compared to pristine CuO NSs. The generation of oxygen due to the catalase (CAT)-like decomposition of H2O2 by CuO@CaO2 NSs resulted in a self-propelled diffusion behavior, characteristic of a H2O2 fueled nanomotor. These nanostructures exhibited both peroxidase (POD)-like and CAT-like activities and were capable of self-production of H2O2 in aqueous media via a chemical reaction between the CaO2 nanoshell and water. Usage of the self-supplied H2O2 by the POD-like activity of CuO@CaO2 NSs amplified the generation of toxic hydroxyl (•OH) radicals, enhancing the chemodynamic effect within the tumor microenvironment (TME). The CAT-like activity provided a source of self-supplied O2 via decomposition of H2O2 to alleviate hypoxic conditions in the TME. Under near-infrared laser irradiation, CuO@CaO2 NSs exhibited photothermal conversion properties, with a temperature elevation of 25 °C. The combined GSH depletion and H2O2 generation led to a more effective production of •OH radicals in the cell culture medium. The chemodynamic function was further enhanced by an elevated temperature. To assess the therapeutic potential, CuO@CaO2 NSs loaded with the photosensitizer, chlorine e6 (Ce6), were evaluated against T98G glioblastoma cells. The synergistic combination of photodynamic, photohermal, and chemodynamic modalities using CuO@CaO2@Ce6 NSs resulted in cell death higher than 90% under in vitro conditions.