Osteoarthritis (OA) is a prevalent and debilitating condition characterized by cartilage destruction and inflammation. Traditional pharmacotherapies for OA are limited by their short-term efficacy and systemic side effects. Radiosynoviorthesis (RSO), involving intra-articular injection of radiopharmaceuticals, has shown promise for OA treatment but is hindered by the toxicity and rapid clearance of radioisotopes. Herein, we propose a novel strategy utilizing metal-organic coordination polymers (MCPs) as carrier of radioactive ¹⁷⁷Lu, with adenosine monophosphate (AMP) as ligand. We then incorporate the MCPs into chitosan/β-glycerophosphate thermosensitive hydrogels (¹⁷⁷Lu/AMP@CG), which demonstrates enhanced retention of ¹⁷⁷Lu in the joint cavity. These hydrogels enable a single-dose intra-articular injection to provide sustained OA treatment without adverse effects. Combining ¹⁷⁷Lu-based RSO with the pharmacological properties of chitosan-based hydrogel yields exceptional anti-inflammatory, cartilage repair and protective effects. Together, this study underscores the significant local retention capacity of the ¹⁷⁷Lu/AMP@CG hydrogel and the potential of anti-inflammatory and chondroprotective strategy toward OA treatment.

中文翻译：

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一种掺入 177Lu 核苷酸配位聚合物的热敏水凝胶，具有抗炎和软骨保护能力，用于治疗骨关节炎


骨关节炎 （OA） 是一种普遍且使人衰弱的疾病，其特征是软骨破坏和炎症。传统的 OA 药物治疗受到其短期疗效和全身副作用的限制。放射性滑膜 （RSO） 涉及关节内注射放射性药物，已显示出治疗 OA 的前景，但受到放射性同位素毒性和快速清除的阻碍。在此，我们提出了一种新的策略，利用金属有机配位聚合物 （MCP） 作为放射性 ¹⁷⁷ Lu 的载体，以单磷酸腺苷 （AMP） 作为配体。然后，我们将 MCP 掺入壳聚糖/β-甘油磷酸盐热敏水凝胶 （ ¹⁷⁷ Lu/AMP@CG） 中，这表明 ¹⁷⁷ Lu 在关节腔中的保留增强。这些水凝胶能够进行单剂量关节内注射，以提供持续的 OA 治疗而不会产生不良反应。将 Lu 基 RSO 与壳聚糖基水凝胶的药理特性相结合 ¹⁷⁷ ，可产生卓越的抗炎、软骨修复和保护作用。总之，这项研究强调了 ¹⁷⁷ Lu/AMP@CG 水凝胶显着的局部保留能力以及抗炎和软骨保护策略对 OA 治疗的潜力。