Abstract
Ratiometric afterglow luminescent (AGL) probes are attractive for in vivo imaging due to their high sensitivity and signal self-calibration function. However, there are currently few ratiometric AGL probes available for imaging enzymatic activity in living organisms. Here, we present an energy diversion (ED) strategy that enables the design of an enzyme-activated ratiometric AGL probe (RAG-RGD) for in vivo afterglow imaging. The ED process provides RAG-RGD with a radiative transition for an 'always on' 520-nm AGL signal (AGL520) and a cascade three-step energy transfer (ET) process for an 'off-on' 710-nm AGL signal (AGL710) in response to a specific enzyme. Using matrix metalloproteinase-2 (MMP-2) as an example, RAG-RGD shows a significant ~11-fold increase in AGL710/AGL520 toward MMP-2. This can sensitively detect U87MG brain tumors through ratiometric afterglow imaging of MMP-2 activity, with a high signal-to-background ratio and deep imaging depth. Furthermore, by utilizing the self-calibration effect of ratiometric imaging, RAG-RGD demonstrated a strong negative correlation between the AGL710/AGL520 value and the size of orthotopic U87MG tumor, enabling accurate monitoring of orthotopic glioma growth in vivo. This ED process may be applied for the design of other enzyme-activated ratiometric afterglow probes for sensitive afterglow imaging.
Overview
- The study presents an energy diversion (ED) strategy for the design of an enzyme-activated ratiometric afterglow probe (RAG-RGD) for in vivo imaging of enzymatic activity in living organisms. The ED process provides RAG-RGD with a radiative transition for an 'always on' 520-nm AGL signal (AGL520) and a cascade three-step energy transfer (ET) process for an 'off-on' 710-nm AGL signal (AGL710) in response to a specific enzyme. The study uses matrix metalloproteinase-2 (MMP-2) as an example and shows a significant ~11-fold increase in AGL710/AGL520 toward MMP-2. The study aims to develop a sensitive afterglow imaging method for detecting U87MG brain tumors through the ratiometric imaging of MMP-2 activity, with a high signal-to-background ratio and deep imaging depth. The study also demonstrates a strong negative correlation between the AGL710/AGL520 value and the size of orthotopic U87MG tumors, enabling accurate monitoring of orthotopic glioma growth in vivo. The study's primary objective is to develop a sensitive and accurate afterglow imaging method for detecting enzymatic activity in living organisms, with the potential for clinical applications in tumor detection and monitoring.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The study identifies a significant ~11-fold increase in AGL710/AGL520 toward matrix metalloproteinase-2 (MMP-2) in response to the energy diversion (ED) process. The study also shows a strong negative correlation between the AGL710/AGL520 value and the size of orthotopic U87MG tumors, enabling accurate monitoring of orthotopic glioma growth in vivo. The study's key findings suggest that the energy diversion (ED) process provides a sensitive and accurate afterglow imaging method for detecting enzymatic activity in living organisms, with the potential for clinical applications in tumor detection and monitoring.
Implications and Future Directions
- The study's findings have significant implications for the field of research or clinical practice. The study demonstrates the potential of the energy diversion (ED) process for the design of other enzyme-activated ratiometric afterglow probes for sensitive afterglow imaging. The study also highlights the potential of ratiometric afterglow imaging for accurate monitoring of orthotopic glioma growth in vivo. The study identifies limitations, such as the need for further optimization of the energy diversion (ED) process and the need for validation in additional animal models and clinical settings. The study suggests future research directions, such as the development of other enzyme-activated ratiometric afterglow probes for sensitive afterglow imaging and the validation of the method in clinical settings.