Artificial nanoenzymes provide a new approach to the treatment of diabetic retinopathy

Recently, the research group of Jiang Zhengxuan, chief physician of the Second Affiliated Hospital of Anhui Medical University, and Wang Xianwen, a professor of Anhui Medical University, published a cover paper in Advanced Functional Materials. They developed an artificial nanoenzyme, iron-quercetin nanoenzyme, and successfully used it in a drug delivery system administered in the retina of mice, providing new ideas for catalytic nanomedicines for the treatment of human diabetic retinopathy and other reactive oxygen species-related diseases.

Schematic diagram of the preparation process of iron-quercetin nanoenzyme Courtesy of the Second Affiliated Hospital of Anhui Medical University

Diabetic retinopathy is a type of diabetic microangiopathy and the leading cause of blindness in adults. According to statistics, there are currently about 120 million diabetic patients in China, of which 30 million to 40 million patients are accompanied by diabetic retinopathy.

However, the exact pathogenesis of diabetic retinopathy remains unclear. Jiang Zhengxuan introduced, “At present, it is generally believed that high blood sugar induces oxidative stress in vivo, mediates irreversible oxidative damage pathways, and overexpression of vascular endothelial growth factor, apoptosis and inflammation, and oxidative stress and its induced high permeability play a crucial role in the pathogenesis of diabetic retinopathy.” ”

Quercetin is an excellent natural antioxidant. However, in clinical application, quercetin has problems such as low bioavailability, poor solubility of body fluids, and large effective concentration. In addition, drug delivery in the posterior segment (i.e., retina or other therapeutic targets) remains a major barrier to drug treatment for fundus lesions.

In this study, the researchers successfully prepared ultra-small iron-quercetin nanoenzymes by coupling quercetin with low-toxic iron ions. “This artificial nanoenzyme can prevent and delay the development and progression of diabetic retinopathy and has excellent mimicry of enzyme activity in organisms including superoxide dismutase, catalase and peroxidase, which are necessary to remove excess reactive oxygen species.” Jiang Zhengxuan said.

Through further experiments, the researchers found that rats provided protection against retinal tissue inflammation and oxidative stress damage, as well as anti-angiogenic effects, after oral administration of low doses of iron-quercetin nanoenzymes. At the same time, compared with the results of another set of experiments, it was found that iron-quercetin nanoenzymes were involved in the regulation of multiple oxidative stress, inflammatory response, anti-angiogenesis and metabolic pathways.

Jiang Zhengxuan believes that the study reveals an artificial nanoenzyme with a variety of intrinsic enzyme properties and significant ability to clear reactive oxygen species, and explores the function and possible mechanism of this nanozyme in the treatment of early diabetic retinopathy. (Source: Wang Min, China Science News)

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