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用于关节软骨退变成像和骨关节炎检测的近红外二区荧光探针。

A NIR-II fluorescent probe for articular cartilage degeneration imaging and osteoarthritis detection.

机构信息

Department of Orthopedics, Zhongnan Hospital of Wuhan University, Number 169, East Lake Road, Wuhan, Hubei 430071, China.

出版信息

Biomater Sci. 2019 Feb 26;7(3):1043-1051. doi: 10.1039/c8bm01440j.

DOI:10.1039/c8bm01440j
PMID:30628591
Abstract

Articular cartilage (AC) is a complex water-bearing tissue consisting of chondrocytes, proteoglycans, and collagen. AC degeneration, which occurs in the early stage and throughout the entire course of osteoarthritis (OA), is one of the main pathological changes of OA. However, current clinical approaches are unable to detect AC degradation during the early stage of OA. Herein, a novel NIR-II probe, CH1055-WL, was developed with an organic fluorophore (CH1055) and type II collagen-binding peptide (WYRGRL) for AC targeting and degeneration imaging. In vitro and in vivo imaging studies demonstrated that CH1055-WL specifically bound to AC and permitted sensitive detection of age-related or surgically induced AC degeneration in living mice. In vitro imaging of cartilage samples from pig knee joint and in vivo imaging of live mice with the probe administered via local injection in joint cavities demonstrated that CH1055-WL specifically and efficiently bound to AC. Further evaluation of CH1055-WL revealed sensitive detection of age-related AC degeneration and surgically induced AC degeneration in living mice. Our results indicated that the cartilage-targeting probe CH1055-WL allowed visual monitoring of AC degeneration in living subjects, thus displaying promise for early OA detection.

摘要

关节软骨(AC)是一种复杂的含水组织,由软骨细胞、蛋白聚糖和胶原组成。AC 退变发生在骨关节炎(OA)的早期和整个过程中,是 OA 的主要病理变化之一。然而,目前的临床方法无法在 OA 的早期阶段检测到 AC 的降解。在此,开发了一种新型近红外二区(NIR-II)探针 CH1055-WL,它由有机荧光团(CH1055)和 II 型胶原蛋白结合肽(WYRGRL)组成,用于 AC 靶向和退变成像。体外和体内成像研究表明,CH1055-WL 特异性结合 AC,并允许在活体小鼠中灵敏检测与年龄相关或手术诱导的 AC 退变。来自猪膝关节软骨样本的体外成像和通过关节腔内局部注射给予探针的活体小鼠的体内成像表明,CH1055-WL 特异性且有效地与 AC 结合。对 CH1055-WL 的进一步评估表明,它能够灵敏地检测活体小鼠与年龄相关的 AC 退变和手术诱导的 AC 退变。我们的结果表明,软骨靶向探针 CH1055-WL 允许在活体受试者中可视化监测 AC 退变,因此有望用于早期 OA 的检测。

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