ROS-Responsive Nanoparticles with Antioxidative Effect for the treatment of Diabetic Retinopathy

Abstract Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes. While current clinical treatments focus on later stages of the disease, early intervention is crucial to impede its progression. Essential oils derived from Fructus Alpiniae zerumbet (EOFAZ) have shown promise in protecting against high glucose (HG)-induced Müller cell activation and the development of DR. In this study, we designed a reactive oxidative species (ROS)-responsive drug delivery system (NPSPHE@EOFAZ) to target early DR stages and combat oxidative stress. Our nanoparticles were engineered to detect and respond to elevated oxidative stress levels, effectively transporting EOFAZ into HG-exposed Müller cells. The NPSPHE@EOFAZ formulation exhibited significant efficacy in inhibiting abnormal cell growth, reducing oxidative stress, and alleviating inflammation in these cells. Moreover, in vivo experiments on diabetic mice with DR demonstrated that NPSPHE@EOFAZ mitigated early pathological changes by reducing oxidative stress and inflammation. Additionally, the NPSPHE@EOFAZ formulation minimized pathological damage in vital organs such as the heart, liver, spleen, lung, and kidney. These results highlight the potential of NPSPHE@EOFAZ as a promising antioxidant for early intervention in DR pathogenesis.