Magnetically Controlled Chlorella-Based Microrobots Loaded with Quercetin for Precision Treatment of Anteromedial Osteoarthritis

Abstract

Anteromedial osteoarthritis (AMOA) is characterized by progressive and irreversible cartilage damage in anteromedial knee joint, and targeted therapies for it are lacking. To address this challenge, a magnetically controlled drug-loaded microrobot is developed based on Chlorella and incorporated quercetin, named M-CH@QUE, which is designed for precise drug delivery targeting AMOA. M-CH@QUE not only alleviated OA symptoms but also protected the cartilage and slowed the progression of AMOA. In vitro experiments demonstrated its excellent biocompatibility, drug-loading capacity, sustained-release properties, and precise control of flat surfaces and joint cartilage using a magnetic actuation system. In addition, the mechanisms are explored underlying the effects of quercetin. It is found that it promoted cell protection by enhancing insulin-like growth factor 1 receptor (IGF1R) phosphorylation and reducing intracellular oxidative stress. In vivo experiments revealed that M-CH@QUE accumulated in the medial knee joint of rats significantly slowed OA progression and effectively protected the cartilage. After 6 and 12 weeks of treatment, the M-CH@QUE significantly reduced both the Osteoarthritis Research Society International (OARIS) score and the Mankin score. In summary, the innovative M-CH@QUE design offers an effective strategy for alleviating AMOA symptoms and slowing the disease progression, thus presenting a highly promising option for treating AMOA.