Antioxidant nanozymes as next-generation therapeutics to free radical-mediated inflammatory diseases: A comprehensive review

Recent developments in exploring the biological enzyme mimicking properties in nanozymes have opened a separate avenue, which provides a suitable alternative to the natural antioxidants and enzymes. Due to high and tunable catalytic activity, low cost of synthesis, easy surface modification, and good biocompatibility, nanozymes have garnered significant research interest globally. Several inorganic nanomaterials have been investigated to exhibit catalytic activities of some of the key natural enzymes, including superoxide dismutase (SOD), catalase, glutathione peroxidase, peroxidase, and oxidase, etc. These nanozymes are used for diverse biomedical applications including therapeutics, imaging, and biosensing in various cells/tissues and animal models. In particular, inflammation-related diseases are closely associated with reactive oxygen and reactive nitrogen species, and therefore effective antioxidants could be excellent therapeutics due to their free radical scavenging ability. Although biological enzymes and other artificial antioxidants could perform well in scavenging the reactive oxygen and nitrogen species, however, suffer from several drawbacks such as the requirement of strict physiological conditions for enzymatic activity, limited stability in the environment beyond their optimum pH and temperature, and high cost of synthesis, purification, and storage make then unattractive for broad-spectrum applications. Therefore, this review systematically and comprehensively presents the free radical-mediated evolution of various inflammatory diseases (inflammatory bowel disease, mammary gland fibrosis, and inflammation, acute injury of the liver and kidney, mammary fibrosis, and cerebral ischemic stroke reperfusion) and their mitigation by various antioxidant nanozymes in the biological system. The mechanism of free radical scavenging by antioxidant nanozymes under in vitro and in vivo experimental models and catalytic efficiency comparison with corresponding natural enzymes has also been presented.