Redox-responsive self-assembled HG-type pectin nanomicelles for alleviating chronic alcoholic liver injury in mice

作者：Lingtao Kang, Chang Xia, Shuangshuang Ma, Zhipeng Gao, Zhipeng Su, Xiaopeng Li, Yifei Zhao, Jiajing Guo, Gaoyang Li · 发表于：Carbohydrate Polymers · 年份：2025 · DOI：10.1016/j.carbpol.2025.123619 · 被引用次数：10 · 研究领域：Alcohol Consumption and Health Effects、Advanced Glycation End Products research、Endoplasmic Reticulum Stress and Disease

This study aimed to develop nanomicelles with redox-responsive properties using HG-type pectin (polygalacturonic acid) as a substrate to enhance the solubility of oleanolic acid (OA) and evaluate their potential application in the prevention of chronic alcoholic liver injury. Three amphiphilic conjugates, PA-OA, PA-S-OA, and PA-SS-OA (PA: polygalacturonic acid; S: 3,3'-thiodipropionic acid; SS: 3,3'-dithiobispropionic acid), were successfully synthesized by carbodiimide chemistry. The amphiphilic conjugates were physicochemically characterized and experimentally validated for efficacy in animal models. In aqueous solutions, these amphiphilic conjugates self-assembled to form nanomicelles with a particle size of approximately 430 nm and excellent stability. These nanomicelles exhibited superior water solubility compared with that of OA. In experiments simulating oxidizing and reducing environments to assess the degradation and OA release, PA-SS-OA exhibited superior redox responsiveness and achieved an efficient controlled release of OA. Erythrocyte hemolysis and cytotoxicity experiments demonstrated the excellent biocompatibility and safety of the prepared nanomicelles. In animal experiments, PA-SS-OA effectively mitigated alcohol-induced chronic liver injury by robustly stimulating the Nrf2 antioxidant response pathway, demonstrating a superior protective capacity compared with that of OA. These findings indicate that PA-SS-OA improves the bioavailability of OA and has poten...