Conditionally Activated ROS Generation by MMP2/9-Specific C₆₀-Based Fluorescence Probes.

Area of Science:

• Bioconjugate Chemistry
• Molecular Imaging
• Photodynamic Therapy

Background:

• Matrix metalloproteinases (MMPs), particularly MMP2 and MMP9, are implicated in tumor progression and metastasis.
• Developing targeted probes for MMPs is crucial for cancer diagnosis and therapy.
• Existing probes often lack sufficient specificity or dual functionality for imaging and treatment.

Purpose of the Study:

• To design and synthesize a C60-coumarin conjugate probe for detecting MMP2/9 activity.
• To evaluate the probe's capability for fluorescence imaging of MMP2/9-expressing cells.
• To assess the probe's potential as a photosensitizer for photodynamic therapy in cancer.

Main Methods:

• Synthesis of a C60-coumarin conjugate linked by an MMP2/9-cleavable peptide.
• Characterization of fluorescence quenching and recovery upon peptide cleavage.
• In vitro cellular imaging experiments using tumor cell lines with varying MMP2/9 expression levels.
• Assessment of photodynamic therapy efficacy based on MMP2/9 activity.

Main Results:

• The C60-coumarin probe exhibited quenched fluorescence, which was restored upon cleavage by MMP2/9.
• Specificity was confirmed using a scrambled peptide control and an MMP2 inhibitor.
• Successful in vitro imaging of MMP2/9 in high-expression DAOY cells was achieved.
• Enhanced 1O2 generation and photocytotoxicity were observed in MMP2/9-expressing cells.

Conclusions:

• The developed probe functions as a specific fluorescent reporter for MMP2/9.
• The probe acts as an effective photosensitizer for MMP2/9-dependent photodynamic therapy.
• This dual-function probe holds promise for targeted cancer imaging and treatment.