title: MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth.
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.
authors.affiliation: Advanced Science Research Center (ASRC), City University New York, 85 St Nicholas Terrace, New York, NY 10031, USA. Electronic address: daniela.kalafatovic@irbbarcelona.org.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kalafatovic
authors.affiliation: CRUK Beatson Institute, Garscube Estate, Glasgow, G61 1BD, UK.
authors.forename: Max
authors.initials: M
authors.lastname: Nobis
authors.affiliation: Advanced Science Research Center (ASRC), City University New York, 85 St Nicholas Terrace, New York, NY 10031, USA; The Graduate Center of the City University of New York, New York, NY 10016, USA.
authors.forename: Jiye
authors.initials: J
authors.lastname: Son
authors.affiliation: CRUK Beatson Institute, Garscube Estate, Glasgow, G61 1BD, UK; The Francis Crick Institute, 215 Euston Road, London NW1 2BE, UK. Electronic address: kurt.anderson@crick.ac.uk.
authors.forename: Kurt I
authors.initials: KI
authors.lastname: Anderson
authors.affiliation: Advanced Science Research Center (ASRC), City University New York, 85 St Nicholas Terrace, New York, NY 10031, USA; WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK; Department of Chemistry and Biochemistry, City University of New York - Hunter College, 695 Park Ave., New York, NY 10065, USA; The Graduate Center of the City University of New York, New York, NY 10016, USA. Electronic address: Rein.Ulijn@asrc.cuny.edu.
authors.forename: Rein V
authors.initials: RV
authors.lastname: Ulijn
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008819:Mice, Nude; D008823:Micelles; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; D004317:Doxorubicin; D020780:Matrix Metalloproteinase 9
keywords: Cancer therapy; MMP; Morphology transition; Peptides; Self-assembly