Electrochemically Responsive Hyaluronic Acid–Functionalized Dendritic Silica Nanoplatform for Delivery of Emodin in Diabetic Nephropathy

Oxidative stress induced by NOX4 overactivation plays a central role in podocyte injury during diabetic nephropathy (DN). In this study, a multifunctional Emodin-loaded nanoparticle system (Emodin-NPs) was designed to target NOX4 and alleviate oxidative damage. The delivery platform was constructed using dendritic mesoporous silica nanoparticles (DMSNs) coated with hyaluronic acid (HA) to enhance cellular targeting. Furthermore, HA was modified with a π-conjugated compound (compound 1) and a green tea–derived bioactive molecule (compound 2), aiming to improve the electrochemical responsiveness and stability of the nanocarrier. Comprehensive characterization confirmed the successful synthesis of the composite material, 1-HA-2@DMSNs@Emodin, which exhibited favorable electrochemical behavior and stable physicochemical properties. In vitro experiments using mouse podocyte MPC5 cells demonstrated that Emodin-NPs significantly alleviated high-glucose-induced injury by enhancing cell viability, downregulating NOX4 mRNA expression, and reducing IL-6 secretion. This work provides a promising and biocompatible nanoplatform for redox-responsive drug delivery and offers a potential strategy for the treatment of diabetic nephropathy.