A dual-targeted nano-system co-regulating macrophage ROS and fibroblast ferroptosis for rheumatoid arthritis treatment.

IF 5.8 3区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Biomaterials Science Pub Date : 2025-07-10 DOI:10.1039/d5bm00618j

Xiaohua Wang, Tingting Gao, Jingjing Wu, Xu Zhou, Yuanyuan Chu, Lei Zhang, Xi Cao

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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a marked macrophage polarization imbalance and abnormal synovial fibroblast proliferation. Herein, we developed a multifunctional drug delivery platform utilizing a glycosaminoglycan heparin derivative. This derivative combines heparin (Hep), which targets macrophages and synovial fibroblasts, with phenylboronic acid (PBA), which exhibits ROS-responsive properties, to regulate macrophage polarization and inhibit synovial fibroblast proliferation. Celastrol (CLT) was encapsulated in multifunctional lipid vesicles (Hep-Lips/CLT) to ameliorate the inflammatory microenvironment. This platform specifically targeted macrophages and synovial fibroblasts, achieving a dual therapeutic effect. Hep-Lips/CLT could serve as an inflammation-targeted therapy, thereby regulating macrophage repolarization, inducing ferroptosis in synovial fibroblasts to inhibit proliferation, and achieving ROS-responsive release. Overall, Hep-Lips/CLT delivery supported by glycosaminoglycan derivatives could be used as a new therapy for RA. Notably, this study presents the first synthetic glycosaminoglycan derivative for preparing multifunctional lipid vesicles to simultaneously target macrophages and synovial fibroblasts, offering an effective RA therapeutic strategy.

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双靶向纳米系统协同调节巨噬细胞ROS和成纤维细胞铁下垂治疗类风湿关节炎。

类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特征是巨噬细胞极化失衡和滑膜成纤维细胞增生异常。在此，我们利用糖胺聚糖肝素衍生物开发了一个多功能药物传递平台。该衍生物将靶向巨噬细胞和滑膜成纤维细胞的肝素（Hep）与具有ros响应特性的苯硼酸（PBA）结合，以调节巨噬细胞极化并抑制滑膜成纤维细胞增殖。Celastrol （CLT）被包裹在多功能脂质囊泡（Hep-Lips/CLT）中以改善炎症微环境。该平台专门针对巨噬细胞和滑膜成纤维细胞，实现双重治疗效果。Hep-Lips/CLT可作为炎症靶向治疗，通过调节巨噬细胞复极化，诱导滑膜成纤维细胞铁上沉抑制增殖，实现ros应答释放。总之，糖胺聚糖衍生物支持的Hep-Lips/CLT递送可以作为一种新的治疗RA的方法。值得注意的是，本研究首次合成了糖胺聚糖衍生物，用于制备多功能脂质囊泡，同时靶向巨噬细胞和滑膜成纤维细胞，提供了一种有效的RA治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomaterials Science MATERIALS SCIENCE, BIOMATERIALS-

CiteScore

11.50

自引率

4.50%

发文量

556

期刊介绍： Biomaterials Science is an international high impact journal exploring the science of biomaterials and their translation towards clinical use. Its scope encompasses new concepts in biomaterials design, studies into the interaction of biomaterials with the body, and the use of materials to answer fundamental biological questions.