The precise detection of pathological type I collagen is critical for diagnosing and prognosticating various diseases such as fibrosis and tumors. Surface-enhanced Raman scattering (SERS) is emerging as a promising high-resolution imaging technique, yet the intricate process of covalently modifying antibodies often results in SERS probes with diminished selectivity. We herein for the first time report the development of dual SERS peptide probes, Ag@R1@PCTP (S-P) and Ag@R2@ICTP (S-I), which integrate collagen targeting peptides (CTPs), Raman reporters, and silver nanoparticles (Ag NPs) for specific imaging of pathological type I collagen in connective tissues. The S-P/S-I dual SERS peptide probes displayed distinct peaks at 2154 cm −1 and 2227 cm −1 in the Raman silent region with no overlap, showcasing their capability for multiplex imaging free from cross-interference. The SERS peptide probe S-P is specifically tuned to target pathological collagen, excluding intact collagen, while S-I effectively recognizes type I collagen in both its pathological and healthy states. The S-P/S-I probes have exhibited outstanding effectiveness in identifying pathological type I collagen across various connective tissues and have been successfully applied for imaging this collagen in a variety of cancer tissues. The innovative dual SERS peptide probes offer a highly specific and robust tool for imaging pathological type I collagen in tissues, presenting significant potential for the accurate diagnosis and treatment of a range of collagen-related diseases.
Hepatic fibrosis, the insidious progression of chronic liver scarring leading to life-threatening cirrhosis and hepatocellular carcinoma, necessitates the urgent development of noninvasive and precise diagnostic methodologies. Denatured collagen emerges as a critical biomarker in the pathogenesis of hepatic fibrosis. Herein, we have for the first time developed 3D-printed collagen capture chips for highly specific surface-enhanced Raman scattering (SERS) detection of denatured type I and type IV collagen in blood, facilitating the early diagnosis of hepatic fibrosis. Employing a novel blend of denatured collagen-targeting peptide-modified silver nanoparticle probes (Ag@DCTP) and polyethylene glycol diacrylate (PEGDA), we engineered a robust ink for the 3D fabrication of these collagen capture chips. The chips are further equipped with specialized SERS peptide probes, Ag@ICTP@R1 (S–I) and Ag@IVCTP@R2 (S–IV), tailored for the targeted detection of type I and IV collagen, respectively. The SERS chip platform demonstrated exceptional specificity and sensitivity in capturing and detecting denatured type I and IV collagen, achieving detection limits of 3.5 ng/mL for type I and 3.2 ng/mL for type IV collagen within a 10–400 ng/mL range. When tested on serum samples from hepatic fibrosis mouse models across a spectrum of fibrosis stages (S0–S4), the chips consistently measured denatured type I collagen and detected a progressive increase in type IV collagen concentration, which correlated with the severity of fibrosis. This novel strategy establishes a benchmark for the multiplexed detection of collagen biomarkers, enhancing our capacity to assess the stages of hepatic fibrosis.
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