Nanocatalytic Antioxidation: A General Chemical Approach for Alleviating Oxidative Stress in Diseases

Conspectus The overexpression of reactive oxygen species (ROS) is one of the major causes of various human diseases, including cardiovascular diseases, neurodegenerative diseases, and multiple inflammations, by initiating local oxidative stress at specific sites. The excessive ROS not only leads to oxidative injury of normal functional cells but also activates immune cells to aggravate inflammation. Therefore, scavenging excessive ROS is a feasible strategy for treating these diseases. Although many molecular drugs (such as N -acetylcysteine and coenzyme Q10) have been approved for antioxidative therapies, from the perspective of chemical reaction, these antioxidant molecules can only act as reactants to react with ROS, leading to a nonsustainable antioxidative effect, largely compromising therapeutic outcome. Our research team has proposed the concept of “nanocatalytic medicine”, which aims to use nanoparticles to trigger catalytic reactions in pathological sites, regulating the concentrations of ROS efficiently and sustainably for disease treatments. Till now, most efforts have been focusing on the development of pro-oxidative nanocatalysts to catalyze ROS generation for tumor therapy, which induces oxidative damage of cancer cells, while the antioxidative nanocatalysts for treating other oxidative stress-related diseases have been less reported, and the chemical strategy of nanocatalytic antioxidation has rarely been discussed specifically, which is in contrast to the conventional nanocatalytic pro-oxidation approach for tumor therapy. During the last several years, our laboratory has developed various catalytic antioxidative nanosystems to trigger nanocatalytic antioxidation reactions for treating multiple diseases, including ischemic cardiomyopathy, diabetic cardiomyopathy, aortic dissection, alcoholic liver injury, inflammatory bowel disease, psoriasis, atopic dermatitis, rheumatoid arthritis, etc. From the perspective of chemical reaction, these nanosystems act as catalysts in antioxidation reactions and therefore will not be consumed but can lead to a sustainable and highly efficient antioxidative effect. Such a strategy not only largely elevates therapeutic efficacy but also reduces the doses of therapeutic agents required for administration. Moreover, the established catalytic antioxidation reactions may modulate the immune microenvironments at pathological sites, resulting in favorable therapeutic outcomes. In this Account, we will discuss the recent advances in our laboratory in the design and fabrication of antioxidative nanocatalysts for various disease treatments, highlighting nanocatalytic antioxidation as a general chemical strategy for alleviating oxidative stress in diseases. The material chemistry of these catalytic antioxidative nanosystems will be elucidated, which underlies elevated therapeutic outcome. It is expected that such a chemical strategy of nanocatalytic antioxidation will make a significant contribution to disease treatments in the future.