MT1-MMP activatable fluorogenic probes with enhanced specificity <i>via</i> high-affinity peptide conjugation for tumor imaging

Ji, Xiuru; Xie, Shuping; Jiao, Yan; Zhang, Xiaojuan; Sun, Duxin; Yang, Victor C.; Wang, Mei; He, Huining; Sun, Lu

doi:10.1039/c9bm02007a

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…One important reason is that both MMP-2 and MMP-9 are extracellularly secreted, soluble types of MMPs. They are abundantly secreted into the bloodstream, providing high background signals, and probes are easily washed away, which thus lowers the imaging quality [36,37]. To compensate for these drawbacks, many reported MMP-2 and MMP-9 probes were designed to carry another recognition sequence to anchor these probes to the extracellular membrane of speci c cells, which increased the technical di culty of probe synthesis, while the effects might not have been as expected [38].…”

Section: Discussionmentioning

confidence: 99%

MMP-14-targeted Nanoprobe for in vivo Fluorescence Imaging of Rupture-prone Carotid Plaques

Han

Liu

Xiao

et al. 2021

Preprint

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Background: The identification of rupture-prone carotid plaques for preventing stroke remains a clinical challenge. Macrophage matrix metalloproteinase (MMP)-14, which contributes to plaque progression and destabilisation, could be a promising biomarker for plaque imaging. This study aimed to design and synthesise an MMP-14-targeted nanoprobe to noninvasively visualise the behaviour of M1 macrophages in atherosclerotic plaques.Methods: A fluorescence molecular imaging probe (AuNPs@PEG-Peptide-Cy5.5) was constructed by covalently attaching the fluorescent dye cyanine (Cy) 5.5, an MMP-14 substrate, and polyethylene glycol (PEG) 5000-wrapped gold nanoparticles (AuNPs), and then administered via tail vein injection to carotid atherosclerosis models for in vivo fluorescence imaging. Additionally, carotid tissues and cultured macrophages were analysed for nanoprobe binding, and MMP-14 and inflammation-related marker expression was evaluated by polymerase chain reaction, western blotting, and immunohistochemistry.Results: MMP-14 expression significantly increased with plaque progression, along with the upregulation of MMP-2 and inflammatory M1 markers, CD68 and F4/80, and significant downregulation of the M2 marker CD206. All of cell, tissue and in vivo fluorescence imaging exhibited a favourable targeting efficacy of AuNPs@PEG-Peptide-Cy5.5 for MMP-14.Conclusions: MMP-14, a cell membrane-anchoring enzyme, can serve as a biomarker of vulnerable plaques, and MMP-14 substrate-based AuNPs@PEG-Peptide-Cy5.5, with an intense fluorescence signal after activation and good biocompatibility, can be applied to screen for and monitor plaque progression in vivo.

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Section: Discussionmentioning

confidence: 99%

MMP-14-targeted Nanoprobe for in vivo Fluorescence Imaging of Rupture-prone Carotid Plaques

Han

Liu

Xiao

et al. 2021

Preprint

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“…In all of those substrate-based strategies and mainly due to the highly conserved structural topology between the different MMPs, the peptide sequence is rarely cleaved by a single MMP. To address this issue, an activatable fluorogenic probe with enhanced specificity for MT1-MMP was recently developed (Ji et al, 2020). In this case, the specificity of the FRET probes is increased by tethering the MT1-MMP peptide sequence to an additional recognition element that binds away from the catalytic cleft.…”

Section: A Substrate-based Probes For a Cleavage Assaymentioning

confidence: 99%

Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology

et al. 2022

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“…Matrix metalloproteinases (MMPs), known as important biomarkers, are a kind of proteases involved in the onset of tumor, invasion, progression, metastasis, and angiogenesis of cancers. [108] Among them, matrix metalloproteinases-2 (MMP-2) is one of the most important, because it is often abnormally expressed in most of the solid tumors in such as bladder, breast, prostate, colon, and stomach cancers, rendering assessing in-vivo MMP-2 activity closely linked to the clinical diagnosis and therapeutic evaluation of cancers. [109,110] Most recently, a few probes that are activatable by MMP-2 have been designed and used for bioimaging applications.…”

Section: Matrix Metalloproteinases-2mentioning

confidence: 99%

Most recent advances on enzyme‐activatable optical probes for bioimaging

Mei

Tian

2021

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Enzymes are essential biological elements that play vital roles in many key cellular events and physiological processes. The dysregulation of enzyme activity broadly occurs in a large number of diseases ranging from inflammation to neurodegenerative disorders to tumors. Molecular imaging allows accurate and noninvasive visualization of biological analytes/physiological processes of interest closely linked to human health at different levels. Among various imaging modalities, optical imaging stands out benefited from its high sensitivity, excellent spatiotemporal resolution, real‐time mode, and facile accessibility. Diverse optical probes specifically activatable by disease‐relevant enzymes have sprung up. In comparison to the “always‐on” counterparts, the “off‐on” imaging probes activated by enzymes hold great promise for precise diagnosis of diseases at early stage with high target‐to‐background ratio, dramatically improved specificity, and significantly enhanced sensitivity. Herein, the most recent advances in optical probes activatable by enzymes for biosensing and bioimaging are briefly reviewed emphasizing their molecular design, working mechanism, and biomedical applications. Besides, some important prospects and the current challenges to fully implement the potential of enzyme‐activatable probes for precise and efficient theranostics in life science are also pointed out to hopefully arouse new insights into the development of new generation of theranostics.

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MT1-MMP activatable fluorogenic probes with enhanced specificity via high-affinity peptide conjugation for tumor imaging

Abstract: A novel MT1-MMP activatable fluorogenic probe for tumor detection with enhanced specificity was developed via high-affinity and specific peptide conjugation.

Cited by 8 publications

References 32 publications

MMP-14-targeted Nanoprobe for in vivo Fluorescence Imaging of Rupture-prone Carotid Plaques

MMP-14-targeted Nanoprobe for in vivo Fluorescence Imaging of Rupture-prone Carotid Plaques

Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology

Most recent advances on enzyme‐activatable optical probes for bioimaging

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