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

Abstract

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...

Approaches to Control and Monitor Protease Levels in Chronic Wounds

“…Protease sensors are of interest for various applications, including the detection of gum diseases, [331] cancer, [332] toxins detection, [333] and quantification of proteases secreted by cells. [334] A review article released in early 2023 discusses publications over the past 3 years related to MMP sensors; [335] some older studies in this field have been reviewed by Kirchhain et al [336] As discussed in 4 previous sections, protease levels could potentially provide some insights into the current or future state of the wounds, and as a result, some researchers targeted the development of protease indicators or sensors with specific applications in wound diagnosis and therapy.…”

Target-induced hot spot construction for sensitive and selective surface-enhanced Raman scattering detection of matrix metalloproteinase MMP-9

“…For example, patients with high levels of MMP-2 and MMP-9 were clinically defined as a poor prognosis [ 10 ]. MMP-9 is therefore introduced as a possible biomarker in light of its potential application in diagnosis and treatment monitoring of tumors’ progression [ 11 ]. The highly sensitive and selective determination of MMPs is important for elucidating the mechanism of disease occurrence and developing cancer diagnosis and treatment strategies at early stage.…”

High-fidelity imaging of a tumour-associated lysosomal enzyme with an acceptor engineering-boosted near-infrared fluorescent probe

“…33,34 In addition, the accessibility of small molecule-based lysosome-targeting probes in living objects remains to be further explored (Table 1), despite the success of nanodevices in mapping lysosomal enzyme activity in vivo. [35][36][37] Given this, it is still challenging and highly desired to develop novel NIR lysosome-targeting probes for specic detection and visualization of biomarkers in vivo.…”