Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

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 × 105 M−1 s−1) and high selectivity for MMP-13 over a set of nine MMPs. To achieve optimal in vivo pharmacoki-netics and tissue penetration, the probe has been further conjugated to a linear L-polyglutamate chain of 30 kDa. The conjugate detects early bio-chemical events that occur in a surgically induced murine model of OA before major histological changes. The nanometric probe is suitable for the moni-toring 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.

Original publication

DOI

10.1002/adfm.201802738

Type

Journal article

Journal

Advanced functional materials

Publisher

Wiley

Publication Date

25/07/2018