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Detecting Basal Myeloperoxidase Activity in Living Systems with a Near-Infrared Emissive "Turn-On" Probe
Lingyan Liu1, Peng Wei2, Wei Yuan1
1Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
Abstract:
Detecting myeloperoxidase (MPO) activity in living organisms is important because MPO contributes to the pathogenesis of many diseases such as rheumatoid arthritis and other inflammatory diseases, artherosclerosis, neurodegenerative disease, and some cancers. However, rapid and effective methods for the detection of basal MPO activity in living systems have not yet been reported. Herein, we report a near-infrared (NIR) emissive "turn-on" probe FD-301 that can specifically bind to MPO and accurately measure MPO activity in living cells and in vivo via a rapid response to initial hypochlorous acid (HOCl), produced by MPO. Notably, FD-301 could detect the basal level of MPO activity in human promyelocytic leukemia cells (HL-60) and could discriminate between MPO high-expression and low-expression cells. Furthermore, FD-301 was successfully applied to in vivo imaging of MPO in MPO-dependent diseases, such as arthritis and inflammatory bowel disease.
Insights
A new probe, FD-301, enables rapid detection of myeloperoxidase (MPO) activity in living cells and organisms. This breakthrough aids in understanding MPO
Area of Science:
- Biomedical Engineering
- Chemical Biology
- Molecular Imaging
Background:
- Myeloperoxidase (MPO) is implicated in various diseases, including inflammatory conditions, atherosclerosis, neurodegenerative disorders, and cancer.
- Current methods for detecting MPO activity in living systems are limited in speed and effectiveness, particularly for basal activity levels.
Purpose of the Study:
- To develop a rapid and sensitive probe for detecting basal myeloperoxidase (MPO) activity in living cells and organisms.
- To establish a tool for distinguishing between cells with varying MPO expression levels.
- To enable in vivo imaging of MPO activity in disease models.
Main Methods:
- Development of a near-infrared (NIR) emissive "turn-on" probe, designated FD-301.
- FD-301 specifically binds to MPO and responds to hypochlorous acid (HOCl) produced by MPO.
- Application of FD-301 for detecting MPO activity in living cells (HL-60) and in vivo models.
Main Results:
- FD-301 demonstrated specific binding to MPO and a rapid "turn-on" response to HOCl.
- The probe successfully detected basal MPO activity in HL-60 cells.
- FD-301 effectively discriminated between cells with high and low MPO expression.
- Successful in vivo imaging of MPO activity in mouse models of arthritis and inflammatory bowel disease.
Conclusions:
- FD-301 is a novel, highly effective probe for real-time detection and imaging of MPO activity.
- This probe facilitates the study of MPO's role in various physiological and pathological processes.
- FD-301 holds potential for diagnosing and monitoring MPO-related diseases.
