MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth. (August 2016)

• Record Type: Journal Article
• Authors: Kalafatovic, Daniela; Nobis, Max; Son, Jiye; Anderson, Kurt I.; Ulijn, Rein V.
• Is Part Of: Biomaterials. Volume 98(2016)
• Page Start: 192
• Page End: 202
• Publication Date: 2016-08
• Subjects: Peptides -- Self-assembly -- MMP -- Cancer therapy -- Morphology transition; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2016.04.039
• Languages: English
• ISSNs: 0142-9612

Abstract

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.