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

Daniela Kalafatovic, Max Nobis, Jiye Son, Kurt I. Anderson, Rein V. Ulijn

Research output: Contribution to journalArticle

70 Citations (Scopus)
36 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)192-202
Number of pages39
JournalBiomaterials
Volume98
Early online date30 Apr 2016
DOIs
Publication statusPublished - 31 Aug 2016

Keywords

  • peptides
  • self-assembly
  • mmp
  • cancer therapy
  • morphology transition

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