Nanozyme cascade reaction system for diabetic retinopathy therapy via glycometabolism and microenvironment regulation

Diabetic retinopathy (DR) is a serious microvascular complication caused by dysregulated glucose metabolism and represents a primary cause of vision loss. Hyperglycemia-induced metabolic disturbances, oxidative stress, and inflammation are key drivers of DR progression. In this study, we developed a nanozyme cascade system by integrating gold nanozymes with glucose oxidase activity and platinum nanozymes exhibiting catalase and superoxide dismutase activities into a metal-organic framework. This composite, referred to as Pt-MOF/Au, was designed to remodel the pathological microenvironment associated with an aberrant glucose metabolism. The surface was modified with hyaluronic acid (Pt-MOF/Au@HA) to enhance the biocompatibility of Pt-MOF/Au. In vitro experiments demonstrated that Pt-MOF/Au@HA effectively decomposed glucose and scavenged excess reactive oxygen species. Cellular assays and studies in a streptozotocin-induced DR animal model revealed that Pt-MOF/Au@HA significantly alleviated retinal hypoxia; suppressed the expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, and pro-inflammatory factors; and reduced vascular leakage. Furthermore, in an oxygen-induced retinopathy mouse model, Pt-MOF/Au@HA inhibited pathological retinal neovascularization while promoting vascular remodeling and normalization. This comprehensive therapeutic strategy that combines glucose reduction, hypoxia alleviation, radical scavenging, and anti-inflammatory effects via a nanozyme cascade system demonstrates robust efficacy in the treatment of DR.