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| Item Type: | Article |
|---|---|
| Title: | In vivo imaging of MMP-13 activity using a specific polymer-FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy |
| Creators Name: | Duro-Castano, A., Lim, N.H., Tranchant, I., Amoura, M., Beau, F., Wieland, H., Kingler, O., Herrmann, M., Nazaré, M., Plettenburg, O., Dive, V., Vicent, M.J. and Nagase, H. |
| Abstract: | Imaging early molecular changes in osteoarthritic (OA) joints is instrumental for the development of disease‐modifying drugs. To this end, a fluorescent resonance energy transfer-based peptide probe that is cleavable by matrix metalloproteinase 13 (MMP-13) has been developed. This protease degrades type II collagen, a major matrix component of cartilage. The probe exhibits high catalytic efficiency (kcat/KM = 6.5 × 105m-1 s-1) and high selectivity for MMP-13 over a set of nine MMPs. To achieve optimal in vivo pharmacokinetics and tissue penetration, the probe has been further conjugated to a linear l-polyglutamate chain of 30 kDa. The conjugate detects early biochemical events that occur in a surgically induced murine model of OA before major histological changes. The nanometric probe is suitable for the monitoring of in vivo efficacy of an orally bioavailable MMP-13 inhibitor, which effectively blocks cartilage degradation during the development of OA. This new polymer-probe can therefore be a useful tool in detecting early OA, disease progression, and in developing MMP-13-based disease-modifying drugs for OA. |
| Keywords: | Early Detection, Live Imaging, MMP‐13 Nanoprobes, Osteoarthritis, Polymer Therapeutics, Animals, Mice |
| Source: | Advanced Functional Materials |
| ISSN: | 1616-301X |
| Publisher: | Wiley-VCH |
| Volume: | 28 |
| Number: | 37 |
| Page Range: | 1802738 |
| Date: | 12 September 2018 |
| Official Publication: | https://doi.org/10.1002/adfm.201802738 |
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