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MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth

Kalafatovic, Daniela and Nobis, Max and Son, Jiye and Anderson, Kurt I. and Ulijn, Rein V. (2016) MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth. Biomaterials, 98. pp. 192-202. ISSN 0142-9612

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Abstract

A central challenge in cancer care is to ensure that therapeutic compounds reach their targets. One approach is to use enzyme-responsive biomaterials, which reconfigure in response to endogenous enzymes that are overexpressed in diseased tissues, as potential site-specific anti-tumoral therapies. Here we report peptide micelles that upon MMP-9 catalyzed hydrolysis reconfigure to form fibrillar nanostructures. These structures slowly release a doxorubicin payload at the site of action. Using both in vitro and in vivo models we demonstrate that the fibrillar depots are formed at the sites of MMP-9 overexpression giving rise to enhanced efficacy of doxorubicin, resulting in inhibition of tumor growth in an animal model.