Journal
BIOMATERIALS
Volume 98, Issue -, Pages 192-202Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.04.039
Keywords
Peptides; Self-assembly; MMP; Cancer therapy; Morphology transition
Funding
- EPSRC
- Cancer Research UK
- Engineering and Physical Sciences Research Council [EP/I004912/1] Funding Source: researchfish
- EPSRC [EP/I004912/1] Funding Source: UKRI
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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 nano structures. 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 over expression giving rise to enhanced efficacy of doxorubicin, resulting in inhibition of tumor growth in an animal model. (C) 2016 The Author(s). Published by Elsevier Ltd.
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