Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, 1201 Welch Rd., Lucas Expansion, P095, Stanford, CA 94305, USA.
Department of Immunology & Rheumatology, School of Medicine, Stanford, CA, USA.
Biomaterials. 2014 Aug;35(26):7511-21. doi: 10.1016/j.biomaterials.2014.05.042. Epub 2014 Jun 7.
Articular cartilage is the hydrated tissue that lines the ends of long bones in load bearing joints and provides joints with a smooth, nearly frictionless gliding surface. However, the deterioration of articular cartilage occurs in the early stages of osteoarthritis (OA) and is clinically and radiographically silent. Here two cationic near infrared fluorescent (NIRF) dipicolylamine (DPA) probes, Cy5-DPA-Zn and Cy7-DPA-Zn, were prepared for cartilage degeneration imaging and OA early detection through binding to the anionic glycosaminoglycans (GAGs). The feasibility of NIRF dye labeled DPA-Zn probes for cartilage degeneration imaging was examined ex vivo and in vivo. The ex vivo studies showed that Cy5-DPA-Zn and Cy7-DPA-Zn not only showed the high uptake and electrostatic attractive binding to cartilage, but also sensitively reflected the change of GAGs contents. In vivo imaging study further indicated that Cy5-DPA-Zn demonstrated higher uptake and retention in young mice (high GAGs) than old mice (low GAGs) when administrated via local injection in mouse knee joints. More importantly, Cy5-DPA-Zn showed dramatic higher signals in sham joint (high GAGs) than OA side (low GAGs), through sensitive reflecting the change of GAGs in the surgical induced OA models. In summary, Cy5-DPA-Zn provides promising visual detection for early cartilage pathological degeneration in living subjects.
关节软骨是一种富含水分的组织，覆盖在承重关节的长骨末端，为关节提供光滑、几乎无摩擦的滑行表面。然而，在骨关节炎（OA）的早期阶段，关节软骨就会发生恶化，而且在临床上和影像学上都是无声无息的。在这里，我们制备了两种阳离子近红外荧光（NIRF）二吡啶基胺（DPA）探针，Cy5-DPA-Zn 和 Cy7-DPA-Zn，用于通过与阴离子糖胺聚糖（GAGs）结合，对软骨退变进行成像和早期检测 OA。通过体外和体内实验，研究了 NIRF 染料标记的 DPA-Zn 探针用于软骨退变成像的可行性。体外研究表明，Cy5-DPA-Zn 和 Cy7-DPA-Zn 不仅表现出对软骨的高摄取和静电吸引力结合，而且还能敏感地反映 GAGs 含量的变化。体内成像研究进一步表明，当通过局部注射到小鼠膝关节中给药时，Cy5-DPA-Zn 在年轻小鼠（高 GAGs）中的摄取和保留率高于老年小鼠（低 GAGs）。更重要的是，Cy5-DPA-Zn 在假手术关节（高 GAGs）中的信号明显高于 OA 侧（低 GAGs），通过敏感地反映手术诱导的 OA 模型中 GAGs 的变化。综上所述，Cy5-DPA-Zn 为活体早期软骨病理性退变提供了有前途的可视化检测方法。
