State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.
Gansu Engineering Research Center of Medical Collagen, Lanzhou, Gansu 730000, P. R. China.
Anal Chem. 2024 Oct 22;96(42):16649-16657. doi: 10.1021/acs.analchem.4c02847. Epub 2024 Oct 7.
Hepatic fibrosis is a common chronic liver disease, and its severe progression can culminate in cirrhosis and hepatocellular carcinoma (HCC). Precise diagnosis and staging of hepatic fibrosis are essential to prevent liver cirrhosis and HCC. Simultaneous detection of multiplex collagen biomarkers within liver tissue is crucial for staging hepatic fibrosis. We herein for the first time constructed multiplex collagen fingerprinting for the staging of hepatic fibrosis using high-precision fluorescence-guided surface-enhanced Raman scattering (SERS) imaging. SERS/fluorescent probes, collectively referred to as SF, comprising silver nanoparticles (Ag NPs), Raman reporters, and FAM-labeled collagen targeting peptides. These probes exhibit exceptional aqueous dispersion and stability, attributed to the increased number of Asp residues in CTP. Meanwhile, SF probes, namely SF-I, SF-IV, and SF-D have demonstrated specific targeting of type I, type IV, and denatured collagen, respectively, within hepatic fibrotic tissues. The results from fluorescence-guided SERS imaging underscore the method's capacity for typing, localization, and quantification of collagen, thus providing novel insights into collagen's role in the development of hepatic fibrosis. The collagen fingerprinting strategy offers a potent toolkit for the multifaceted profiling of collagen superfamilies, holding significant implications for the precise staging of hepatic fibrosis.
肝纤维化是一种常见的慢性肝病，其严重进展可导致肝硬化和肝细胞癌（HCC）。精确诊断和分期肝纤维化对于预防肝硬化和 HCC 至关重要。同时检测肝组织内的多种胶原生物标志物对于肝纤维化的分期至关重要。我们首次构建了使用高精度荧光引导的表面增强拉曼散射（SERS）成像进行肝纤维化分期的多聚胶原指纹图谱。SERS/荧光探针，统称为 SF，由银纳米颗粒（Ag NPs）、拉曼报告分子和 FAM 标记的胶原靶向肽组成。这些探针表现出出色的水相分散性和稳定性，这归因于 CTP 中增加的 Asp 残基数量。同时，SF 探针，即 SF-I、SF-IV 和 SF-D，已证明在肝纤维化组织中分别针对 I 型、IV 型和变性胶原具有特异性靶向性。荧光引导 SERS 成像的结果强调了该方法对胶原进行分型、定位和定量的能力，从而为胶原在肝纤维化发展中的作用提供了新的见解。胶原指纹图谱策略为胶原超家族的多方面分析提供了有力的工具，对肝纤维化的精确分期具有重要意义。
