In vivo imaging of MMP-13 activity using a specific polymer-FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy

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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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