TiO_x(OH)_4-2x Nanosheets with Catalytic Antioxidative Activity Alleviate Oxidative Injury in Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) is one of the most lethal complications of diabetes and is induced by the overproduction of reactive oxygen species (ROS) in cardiomyocytes due to sustained high glucose levels, leading to cardiac oxidative damage and final sudden death. Drugs and antioxidants currently applied to the clinical therapy of DCM fail to scavenge ROS efficiently, resulting in compromised therapeutic efficacy. Herein, a nanocatalytic antioxidative therapeutic strategy is proposed for DCM treatment. A two-dimensional TiO_x(OH)_4-2x nanosheet platform has been constructed with efficient ROS-scavenging activity, which can catalyze antioxidation reaction through redox cycling between Ti^IV/Ti^III accompanied by inner-sphere two-electron transfer. Cellular experiments demonstrate that the TiO_x(OH)_4-2x nanosheet can not only protect cardiomyocytes from oxidative damage induced by a high glucose environment but also alleviate inflammation to further protect cardiomyocytes from inflammatory injury. The in vivo animal model confirms that the nanosheet alleviates myocardial oxidative injury and recovers cardiac function. Such a nanocatalytic antioxidation strategy is expected to provide a feasible approach for treating DCM and other cardiovascular diseases.