Mass-Encoded Suspension Array for Multiplex Detection of Matrix Metalloproteinase Activities

Hu, Junjie; Liu, Fei; Chen, Yunlong; Fu, Jia; Shangguan, Guoqiang; Ju, Huangxian

doi:10.1021/acs.analchem.2c00854

Cited by 9 publications

(13 citation statements)

References 40 publications

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“…Therefore, sensitive detection of MMP-2 is of great necessity in early disease diagnosis and therapy. Recently, some analytical technologies like mass spectrometry, 4 electrochemistry, 5 and Raman spectroscopy 6 have been applied in protein detection. However, the above testing methods exhibited certain shortcomings of low sensitivity, complex operation and expensive equipment.…”

Section: ■ Introductionmentioning

confidence: 99%

Nitrogen-, Sulfur-, and Fluorine-Codoped Carbon Dots with Low Excitation Potential and High Electrochemiluminescence Efficiency for Sensitive Detection of Matrix Metalloproteinase-2

et al. 2023

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In this study, nitrogen-, sulfur-, and fluorine-codoped carbon dots (NSF-CDs) with high electrochemiluminescence (ECL) efficiency were developed as novel emitters to fabricate an ECL biosensor for sensitive detection of matrix metalloproteinase 2 (MMP-2). Impressively, compared to previously reported CDs, NSF-CDs with narrow band gap not only decreased the excitation voltage to reduce the side reaction and the damage on biomolecules but also had hydrogen bonds to vastly enhance the ECL efficiency. Furthermore, an improved exonuclease III (Exo III)-assisted nucleic acid amplification method was established to convert trace MMP-2 into a mass of output DNA, which greatly improved the target conversion efficiency and ECL signal. Hence, the ECL biosensor has realized the sensitive detection of MMP-2 proteins from 10 fg/mL to 10 ng/mL with a limit of detection of 6.83 fg/mL and has been successfully applied in the detection of MMP-2 from Hela and MCF-7 cancer cells. This strategy offered neoteric CDs as ECL emitters for sensitive testing of biomarkers in medical research.

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Section: ■ Introductionmentioning

confidence: 99%

Nitrogen-, Sulfur-, and Fluorine-Codoped Carbon Dots with Low Excitation Potential and High Electrochemiluminescence Efficiency for Sensitive Detection of Matrix Metalloproteinase-2

et al. 2023

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“…In another example, Hu et al reported the development of a mass spectrometric biosensing strategy for multiplex detection the activity of MMP-2 and MMP-7 (Figure 13b). [86] The sensor was developed by coating the nickel-nitrilotriacetic acid-modified magnetic beads (Ni-NTA MBs) with MMP-specific peptideisobaric tags for relative and absolute quantification (iTRAQ) conjugates through the specific binding between Ni-NTA and hexahistidine tag. In this sensor, the iTRAQ 114 and iTRAQ 117 were used for MMP-2 and MMP-7 detection, respectively, and iTRAQ 115 served as the control.…”

Section: Ms Sensorsmentioning

confidence: 99%

Section: Enzymatic Activity‐based Sensorsmentioning

confidence: 99%

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Recent Development and Applications of Sensors for the Detection of Matrix Metalloproteinases

Zhang

et al. 2023

Adv Materials Technologies

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of ECM cleavage. As the number of identified MMPs types increased, researchers began to classify the MMPs according to the protein structure. [3] Despite some structural differences, most of the structural modules of MMPs are still conservative, including i) an amino-terminal peptide which can leads MMPs to the endoplasmic reticulum, ii) a propeptide region (companying with a zinc-interacting thiol group) and a zinc-binding site which can maintains MMPs as inactive zymogens or as a catalytic domain, iii) a linker region of varying residue length that may determine the substrates to which the MMPs can accommodate, and iv) a hemopexin-like domain. [4] With the application of engineered genetic models these years, more biological roles of MMPs have been revealed in recently years. For example, through investigating MMPs' substrates of other proteins, such as pro-proteases, chemokines, antimicrobial peptides, cell surface proteins, coagulation factors, adhesion molecules, cryptic growth factors, and cytokines, [5] it has been revealed that the MMPs have a broad and dramatic impact on physiological processes, for example, immunity, [6] tissue repair, [7,8] cell differentiation, [9,10] and cell invasion. [11] In these physiological processes, MMPs are secreted as zymogens. [12] The cysteine (Cys) residues of MMPs' propeptide regions are able to interact with Zn 2+ of the catalytic domains. The formation of the thiols-Zn 2+ bonds play important roles in maintaining the inactivity of MMPs, i.e., MMPs' activations are achieved by breaking these bonds. It is conceivable that MMPs can be activated by a variety of endogenous or exogenous substances, such as mercurial compounds and chaotropic agents. [4] To regulate the activity of MMPs, organisms have evolved a family of two-domain proteins (TIMPs) as the endogenous inhibitors. [13] Most MMPs are ubiquitously secreted in mammalian organisms. The level of MMPs' expression is generally low under normal physiological conditions, while the abnormally elevated expression and activity levels are often associated with diseases. For example, as of the positive roles of MMPs in tumor growth and angiogenesis, [14] recent studies revealed that MMPs overexpression is implicated in a variety of cancers. [15] MMP-2 and MMP-9 are overexpressed in breast cancer, [16] cervical cancer, [17] etc., while MMP-7 are correlated with colorectal cancer (CRC). [18] Moreover, the prognostic value of MMPs has also been well demonstrated in treatment of different cancers. [19,20] For example, patients with high levels of MMP-2 and MMP-9 were clinically defined as a poor prognosis. [21] Therefore, MMPs' Matrix metalloproteinases (MMPs) are a class of zinc-dependent endopeptidases that play important roles in disease progression. High expression of MMPs is associated with various diseases, including cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. For better understanding the roles of MMPs in these diseases' development and the potential in early diagnosis and treatment m...

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“…In order to overcome the bottleneck for multiplex enzyme activity assays, our group proposed “mass spectrometric biosensing” as a powerful tool for multiplex analysis with mass-tag probes, which could transfer the target information to explicit mass spectrometric signals . This idea was successfully applied to the detection of MMP activities with a mass-encoded suspension array by ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) . The proposed method made use of the relative decrease of peak area ratios of coding regions to detection target MMP-2 and MMP-7 activities.…”

Section: Introductionmentioning

confidence: 99%

Signal-On Mass Spectrometric Biosensing of Multiplex Matrix Metalloproteinases with a Phospholipid-Structured Mass-Encoded Microplate

Liu

Chen

et al. 2023

Anal. Chem.

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The detection of matrix metalloproteinases (MMPs) is of great importance for diagnosis and staging of cancer. This work proposed a signal-on mass spectrometric biosensing strategy with a phospholipid-structured mass-encoded microplate for assessment of multiplex MMP activities. The designed substrate and internal standard peptides were subsequently labeled with the reagents of isobaric tags for relative and absolute quantification (iTRAQ), and DSPE-PEG(2000)maleimide was embedded on the surface of a 96-well glass bottom plate to fabricate the phospholipid-structured mass-encoded microplate, which offered a simulated environment of the extracellular space for enzyme reactions between MMPs and the substrates. The strategy achieved multiplex MMP activity assays by dropping the sample in the well for enzyme cleavages, followed by adding trypsin to release the coding regions for ultrahigh performance liquid chromatography–tandem mass spectrometric (UHPLC–MS/MS) analysis. The peak area ratios of released coding regions and their respective internal standard (IS) peptides exhibited satisfied linear ranges of 0.05–50, 0.1–250, and 0.1–100 ng mL–1 with the detection limits of 0.017, 0.046, and 0.032 ng mL–1 for MMP-2, MMP-7, and MMP-3, respectively. The proposed strategy demonstrated good practicability in inhibition analysis and detections of multiplex MMP activities in serum samples. It is of great potential for clinical applications and can be expanded for multiplex enzyme assays.

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Mass-Encoded Suspension Array for Multiplex Detection of Matrix Metalloproteinase Activities

Cited by 9 publications

References 40 publications

Nitrogen-, Sulfur-, and Fluorine-Codoped Carbon Dots with Low Excitation Potential and High Electrochemiluminescence Efficiency for Sensitive Detection of Matrix Metalloproteinase-2

Nitrogen-, Sulfur-, and Fluorine-Codoped Carbon Dots with Low Excitation Potential and High Electrochemiluminescence Efficiency for Sensitive Detection of Matrix Metalloproteinase-2

Recent Development and Applications of Sensors for the Detection of Matrix Metalloproteinases

Signal-On Mass Spectrometric Biosensing of Multiplex Matrix Metalloproteinases with a Phospholipid-Structured Mass-Encoded Microplate

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