A 177Lu-nucleotide coordination polymer-incorporated thermosensitive hydrogel with anti-inflammatory and chondroprotective capabilities for osteoarthritis treatment

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.