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

44 Citations (Scopus)

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.
LanguageEnglish
Pages192-202
Number of pages39
JournalBiomaterials
Volume98
Early online date30 Apr 2016
DOIs
Publication statusPublished - 31 Aug 2016

Fingerprint

Nanofibers
Matrix Metalloproteinases
Doxorubicin
Self assembly
Tumors
Enzymes
Nanostructures
Micelles
Biocompatible Materials
Growth
Biomaterials
Peptides
Hydrolysis
Neoplasms
Animals
Animal Models
Tissue
Therapeutics
In Vitro Techniques

Keywords

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

Cite this

Kalafatovic, Daniela ; Nobis, Max ; Son, Jiye ; Anderson, Kurt I. ; Ulijn, Rein V. / MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth. In: Biomaterials. 2016 ; Vol. 98. pp. 192-202.
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MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth. / Kalafatovic, Daniela; Nobis, Max; Son, Jiye; Anderson, Kurt I.; Ulijn, Rein V.

In: Biomaterials, Vol. 98, 31.08.2016, p. 192-202.

Research output: Contribution to journalArticle

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