A Theranostic Cathepsin Activity-Based Probe for Noninvasive Intervention in Cardiovascular Diseases

基于组织蛋白酶活性的诊断探针,用于心血管疾病的非侵入性干预

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作者:Tommy Weiss-Sadan, Yael Ben-Nun, David Maimoun, Emmanuelle Merquiol, Ihab Abd-Elrahman, Israel Gotsman, Galia Blum

Conclusions

Photodynamic therapy guided by cysteine cathepsin activity is an effective approach to reduce vascular inflammation and attenuate atherosclerosis progression. This approach could potentially be applied in clinical settings.

Methods

We tested the application of this approach in LDL receptor-deficient mice and used non-invasive imaging and heart cross-section staining to assess the theranostic efficacy of this probe. Moreover, we used fresh human endarterectomy tissues to analyze cathepsin signals on gel, and verified cathepsin identity by mass spectrometry.

Results

We showed that our PS-qABP can rapidly accumulate in areas of inflammatory atheromas in vivo, and application of light therapy profoundly reduced lesional immune cell content without affecting smooth muscle cell and collagen contents. Lastly, using human tissue samples we provided proof-of-concept for future clinical applications of this technology. Conclusions: Photodynamic therapy guided by cysteine cathepsin activity is an effective approach to reduce vascular inflammation and attenuate atherosclerosis progression. This approach could potentially be applied in clinical settings.

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