Rheumatoid arthritis (RA) is a complex autoimmune disease associated with synovial inflammation and articular cartilage destruction. Currently, high-efficiency low-toxicity management of this intractable disease is highly urgent. Here, a drug-backboned polymer, polyglycyrrhetinic acid (PGA), was synthesized through the condensation of GA, a principal anti-inflammatory component of . PGA was then used as a therapeutic polyprodrug carrier to fabricate carrier-free PGA@Cel nanoparticles (NPs) for treating rheumatoid arthritis. The as-prepared NPs exhibited a uniformly spherical morphology with an average particle size of approximately 180 nm and a celastrol (Cel) loading capacity of around 4.5 %. Upon intravenous injection, the NPs demonstrated prolonged blood circulation, efficient accumulation at inflammatory joints through extravasation via leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS) effect. The present study demonstrated enhanced anti-inflammatory and rheumatic decay efficiency in rat models of antigen-induced arthritis, while simultaneously minimizing off-target toxicity. Overall, our results elucidate that this carrier-free drug-backboned nanopolydrug platform provides a promising strategy for RA therapy.

中文翻译：

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无载体聚甘草次酸促进雷公藤红素纳米粒子高效低毒治疗类风湿性关节炎

类风湿性关节炎（RA）是一种与滑膜炎症和关节软骨破坏相关的复杂自身免疫性疾病。当前，对这一疑难杂症的高效低毒治理刻不容缓。在此，通过缩合 GA（主要抗炎成分）合成了一种药物骨架聚合物聚甘草次酸 (PGA)。然后使用 PGA 作为治疗性聚前体药物载体来制造无载体的 PGA@Cel 纳米粒子（NP），用于治疗类风湿性关节炎。所制备的纳米粒子表现出均匀的球形形态，平均粒径约为 180 nm，雷公藤红素 (Cel) 负载量约为 4.5%。静脉注射后，纳米颗粒表现出延长的血液循环，通过渗漏的脉管系统外渗在炎症关节处有效积聚，以及随后的炎症细胞介导的隔离（ELVIS）效应。目前的研究表明，在抗原诱导的关节炎大鼠模型中，抗炎和风湿腐烂的效率得到提高，同时最大限度地减少脱靶毒性。总的来说，我们的结果阐明了这种无载体药物支撑的纳米多药平台为 RA 治疗提供了一种有前景的策略。