Ultrasmall Coordination Polymer Nanodots Fe-Quer Nanozymes for Preventing and Delaying the Development and Progression of Diabetic Retinopathy

摘要

Diabetic retinopathy (DR) is the most prevalent type of retinal vasculopathyand the most widespread cause of preventable blindness in adults. Excessiveincreases in reactive oxygen species (ROS) and vascular endothelialgrowth factor are major initiators and drivers of DR progression, respectively.However, current DR treatment options remain limited, particularlyfor early DR. Nanotechnology-mediated antioxidant strategies are gainingincreasing popularity to treat ocular diseases. Quercetin has excellent ROSscavenging efficiency but poor stability and low bioavailability in physiologicalenvironments. In this study, ultrasmall Fe-Quer nanozymes (NZs) formedby coupling quercetin with low-toxic iron ions are reported that can mimicthe activities of three important antioxidant enzymes, superoxide dismutase,catalase, and peroxidase, thereby exhibiting excellent water dispersion andefficient ROS scavenging ability. In vitro and in vivo assays validate the effectsof Fe-Quer NZs against inflammation, oxidative stress damage, microvascularleakage, and angiogenesis, particularly their vascular protective effectin early DR. Transcriptomic analysis further reveals a potential multitargetspecifictherapeutic mechanism of Fe-Quer NZs against DR. These observationsopen avenues for Fe-Quer NZs, composed of molecules of a naturalproduct and metal ions with artificial NZ activity, as microvascular protectiveagents for DR and other ROS-related diseases.