Many cancer cells have elevated levels of matrix metalloproteinases (MMPs), which are closely implicated in tumor growth and invasion.  The most common MMP-related anticancer approach is the development of MMP-sensitive materials for stimuli-responsive drug release.  Herein, we report the synthesis and characterization of MMP-sensitive iridium(III)-based PEG-peptide hydrogels.  These strongly luminescent hydrogels were prepared through the inverse electron-demand Diels–Alder (IEDDA) reaction of 1) a 4-arm PEG polymer bearing four terminal tetrazine units, 2) an MMP-sensitive peptide containing two bicyclo[6.1.0]nonyne units in its both ends, and 3) a non-emissive iridium(III) bis-tetrazine complex [Ir(dptz)2(Ph2-phen)](Cl).  The hydrogels are prone to degradation by MMPs excreted from cancer cells, resulting in the release of luminescent iridium(III) complex fragments that show interesting (photo)cytotoxicity and inhibition effects on cell migration and invasion.  The enzyme sensitivity and specificity, and biological properties of these luminescent hydrogels will be presented.

We thank the Hong Kong Research Grants Council (CityU 11302820) for financial support.

Reference

Yip, A. M.-H.; Lai, C. K.-H.; Yiu, K. S.-M.; Lo, K. K.-W. Angew. Chem. Int. Ed. 2022, 61, e202116078.