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Hepatic fibrosis, a chronic liver response to injury with potential severe outcomes like cirrhosis and liver cancer, necessitates urgent noninvasive diagnostic techniques to halt disease progression. We herein for the first time developed a single-chain peptide probe targeting pathological collagen for in vivo magnetic resonance imaging (MRI) of hepatic fibrosis. The novel (GhypO) 10 probe, distinguished by its unique monomeric conformation achieved through Pro to (2 S ,4 S )-hydroxyproline (hyp) substitution and subsequent disruption of hydrogen bonding, exhibits selectivity for pathological collagen over its intact counterpart in connective tissues. Fluorescence imaging of liver specimens from fibrotic models displayed a discernible relationship between pathological collagen levels and fibrosis stage. Moreover, T1-weighted MR images post Gd-GhypO administration revealed progressive signal enhancement congruent with fibrosis severity, corroborated by a corresponding increase in the contrast-to-noise ratio (ΔCNR). Biodistribution analysis indicates that Gd-GhypO has low Gd retention in the main organs 24 h postinjection, ensuring the probe's safety for molecular imaging. The Gd-GhypO probe therefore emerges as a potent tool for the precise, noninvasive delineation of hepatic fibrosis stages, offering significant implications for the diagnosis and management of liver fibrosis.

Osteogenesis imperfecta (OI) is a hereditary skeletal disorder characterized by bone fragility and deformities, primarily attributed to defects in type I collagen, the most abundant structural protein in humans. Multiple phosphorylation sites have been detected within collagen, suggesting that phosphorylation may influence mineralization processes, thereby impacting the development of OI. In this study, we investigated the modulation of biomineralization morphology by phosphorylated collagen peptides mimicking Gly-Ser mutations in osteogenesis imperfecta. A series of collagen peptide sequences, including GPO 13 S, GPO 13 pS, GPO 12 S, GPO 12 pS, GPO 11 S, and GPO 11 pS, were synthesized to explore the role of phosphorylation in peptide stability and its templating effect on biomineralization. The CD results indicated that the phosphorylation of Gly-pSer mutants reduces the stability of collagen peptides. SEM images revealed that phosphorylated peptides acted as templates, guiding the morphology of calcium carbonate into either olive-like or spherical structures, depending on their conformational state of the peptides. Non-phosphorylated peptides maintained a calcite crystal structure. The XRD patterns predominantly exhibited peaks associated with calcite and vaterite for GPO 13 pS-CaCO 3 , GPO 12 pS-CaCO 3 , and GPO 11 pS-CaCO 3 , and peaks associated with calcite for GPO 13 S-CaCO 3 , GPO 12 S-CaCO 3 , and GPO 11 S-CaCO 3 , indicating a transformation of mesocrystals influenced by peptide phosphorylation. Our findings elucidate the crucial role of phosphorylated collagen peptides in mediating biomineralization morphology and polymorph selection, offering insights into the complex pathophysiology of OI.

We herein report the construction of a robust MRI peptide contrast agent Gd-ICTP with superior selectivity for type I collagen, enabling the accurate and non-invasive detection of hepatic fibrosis in vivo .

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.

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.

The accurate detection of multiplex collagen biomarkers is vital for diagnosing and treating various critical diseases such as tumors and fibrosis. Despite the attractive optical properties of quantum dots (QDs), it remains technically challenging to create stable and specific QDs-based probes for multiplex biological imaging. We report for the first time the construction of multi-color QDs-based peptide probes for the simultaneous fingerprinting of multiplex collagen biomarkers in connective tissues. A bipeptide system composed of a glutathione (GSH) host peptide and a collagen-targeting guest peptide (CTP) has been developed, yielding CTP-QDs probes that exhibit exceptional luminescence stability when exposed to ultraviolet irradiation and mildly acidic conditions. The versatile bipeptide system allows for facile one-pot synthesis of high-quality multicolor CTP-QDs probes, exhibiting superior selectivity in targeting critical collagen biomarkers including denatured collagen, type I collagen, type II collagen, and type IV collagen. The multicolor CTP-QDs probes have demonstrated remarkable efficacy in simultaneously fingerprinting multiple collagen types in diverse connective tissues, irrespective of their status, whether affected by injury, diseases, or undergoing remodeling processes. The innovative multicolor CTP-QDs probes offer a robust toolkit for the multiplex fingerprinting of the collagen suprafamily, demonstrating significant potential in the diagnosis and treatment of collagen-related diseases., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Jianxi Xiao reports was provided by National Natural Science Foundation of China. Jianxi Xiao reports was provided by Natural Science Foundation of Gansu Province. Xiangdong Cai reports was provided by China Postdoctoral Science Foundation., (© 2024 The Authors.)

Multiplex fluorescence imaging plays a vital role in precision medicine for targeting complex diseases with diverse biomolecular signatures. Quantum dot (QD) probes with vibrant colors are promising candidates for multiplex imaging, but their stability and specificity are frequently compromised by the current tedious post-modification process. We have herein developed a robust and versatile host-guest peptide (HGP) toolbox for creating highly stable and specific QD-based peptide probes for imaging extracellular matrices and cells. The HGP system comprises a host peptide and a guest peptide with a shared sequence pattern of cysteine and negatively charged amino acids, allowing for QD stabilization and specificity towards targeted biomarkers. HGP has been demonstrated as a convenient one-step approach to construct hydrophilic QD-based peptide probes with superior stability under various conditions. Six multicolor HGP-modified QDs have been developed to specifically target extracellular matrix proteins such as collagen, laminin, and nidogen, as well as major cellular elements like the membrane, nucleus, and cytoplasm, providing an efficient tool for real-time monitoring of high-resolution interactions between cancer cells and the extracellular matrix. The HGP system represents a next-generation approach to developing QDs with unprecedented stability and specificity, holding great potential in multiplex imaging and precision medicine.

We herein report the construction of a robust MRI peptide contrast agent Gd-ICTP with superior selectivity for type I collagen, enabling the accurate and non-invasive detection of hepatic fibrosis in vivo .

The development of novel assays to detect collagen fragments is of utmost importance for diagnostic, prognostic and therapeutic decisions in various collagen-related diseases, and one essential question is to discover probe peptides that can specifically recognize target collagen sequences. Herein we have developed the fluorescence self-quenching assay as a convenient tool to screen the capability of a series of fluorescent probe peptides of variable lengths to bind with target collagen peptides. We have revealed that the targeting ability of probe peptides is length-dependent, and have discovered a relatively short probe peptide FAM-G(POG) 8 capable to identify the target peptide. We have further demonstrated that fluorescence self-quenching assay together with this short probe peptide can be applied to specifically detect the desired collagen fragment in complex biological media. Fluorescence self-quenching assay provides a powerful new tool to discover effective peptides for the recognition of collagen biomarkers, and it may have great potential to identify probe peptides for various protein biomarkers involved in pathological conditions., (Copyright © 2017 Elsevier B.V. All rights reserved.)