Bioengineered chondrocyte membrane-camouflaged anti-ferroptotic drug-loaded liposomes: A highly effective cartilage-targeted drug delivery system for osteoarthritis treatment

Osteoarthritis (OA) is a chronic degenerative joint disorder that severely impacts patients' quality of life. Despite various drug treatment strategies, achieving effective therapeutic outcomes remains challenging due to the joint's unique structure, which results in rapid drug clearance through synovial fluid and the dense, avascular cartilage matrix. To address this issue, we developed an innovative nanoplatform utilizing biomimetic cell membrane-coating technology. This bioengineered chondrocyte membrane-camouflaged, anti-ferroptotic, drug- loaded system enhances cartilage penetration, prolongs drug retention, and provides targeted therapy. As a nanovehicle, it targets chondrocytes through membrane fusion, allowing rapid penetration and mitigating OA progression. In vitro experiments show that this nanocarrier alleviates iron homeostasis imbalance and suppresses lipid peroxidation, helping ameliorate metabolic disorders in chondrocytes and addressing multiple pathological processes triggered by ferroptosis. In vivo results further suggest that this "Trojan Horse" strategy extends drug retention in joints and improves therapeutic efficacy. This study presents a potential universal nanoplatform comprising bioengineered chondrocyte membrane-coated liposomes for highly effective cartilage-targeted drug delivery in OA treatment.