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
Çağıl Zeynep Süngü Akdoğan, Esin Akbay, Mehmet Ali Onur, Selis Önel, Alï Tuncel
Abstract
High Resolution Image Download MS PowerPoint Slide 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 CaO 2 nanoshell (CuO@CaO 2 NSs) yielded a nanozyme capable of Cu(I)/Cu(II) redox cycling. Activation of the Cu(I)/Cu(II) cycle by exogenously generated H 2 O 2 from the CaO 2 nanoshell significantly enhanced glutathione (GSH) depletion. CuO@CaO 2 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 H 2 O 2 by CuO@CaO 2 NSs resulted in a self-propelled diffusion behavior, characteristic of a H 2 O 2 fueled nanomotor. These nanostructures exhibited both peroxidase (POD)-like and CAT-like activities and were capable of self-production of H 2 O 2 in aqueous media via a chemical reaction between the CaO 2 nanoshell and water. Usage of the self-supplied H 2 O 2 by the POD-like activity of CuO@CaO 2 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 O 2 via decomposition of H 2 O 2 to alleviate hypoxic conditions in the TME. Under near-infrared laser irradiation, CuO@CaO 2 NSs exhibited photothermal conversion properties, with a temperature elevation of 25 °C. The combined GSH depletion and H 2 O 2 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@CaO 2 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@CaO 2 @Ce6 NSs resulted in cell death higher than 90% under in vitro conditions.