Hyaluronanized gold nanoparticles functionalized with CTX-II antibody for early diagnosis and treatment of knee osteoarthritis

Abstract

Knee osteoarthritis (KOA) is a prevalent degenerative joint disease that leads to disability. Early diagnosis and intervention can significantly delay KOA progression and improve therapeutic outcomes, yet there is still a lack of effective strategies for the early diagnosis and treatment of KOA. The C-terminal cross-linked telopeptides of type II collagen (CTX-II) is a degradation product of type II collagen in the cartilage matrix under the action of matrix metalloproteinases, serving as an important early diagnostic biomarker of KOA. However, the application of CTX-II is hindered by its fluctuating levels in peripheral body fluids. In this study, we utilized the in situ accumulation of CTX-II in early degenerative cartilage, to develop an integrated diagnostic and therapeutic agent, hyaluronic acid-gold nanoparticles conjugated with CTX-II antibody (HAuNP-CAb). HAuNP-CAb can target and accumulate in the damaged cartilage, enhance imaging contrast, thus enabling the visualization of otherwise invisible (damaged) cartilage in X-ray or CT scans. Additionally, we modified HAuNP-CAb with Cy3 (Cy3-HAuNP-CAb) to achieve fluorescent tracing of early degenerative cartilage regions, offering a novel strategy for the detection of early-stage degenerative cartilage during arthroscopic examinations. The aggregation of Cy3-HAuNP-CAb in degenerative cartilage also exerts an anti-inflammatory therapeutic effect by modulating the IL-17 signaling pathway and downregulating the expression of MMP-13 in chondrocytes, preventing the degradation of the cartilage matrix. Intra-articular injection of Cy3-HAuNP-CAb in rat OA model achieved better therapeutic efficacy as compared to other treatment groups, manifested by lower OARSI and synovitis scores, and more type II collagen deposition. In summary, we reported a feasible approach for in situ targeting of cartilage CTX-II, providing potential new strategies for the clinical diagnosis and treatment of early KOA.