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

Kalafatovic, Daniela and Nobis, Max and Son, Jiye and Anderson, Kurt I. and Ulijn, Rein V. (2016) MMP-9 triggered self-assembly of doxorubicin nanofiber depots halts tumor growth. Biomaterials, 98. pp. 192-202. ISSN 1878-5905 (https://doi.org/10.1016/j.biomaterials.2016.04.039)

[thumbnail of Kalafatovic-etal-B2016-MM9-triggered-self-assembly-of-doxorubicin-nanofiber]
Preview
 Text. Filename: Kalafatovic_etal_B2016_MM9_triggered_self_assembly_of_doxorubicin_nanofiber.pdf
Accepted Author Manuscript
Download (1MB)| Preview

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.

ORCID iDs

Kalafatovic, Daniela, Nobis, Max, Son, Jiye, Anderson, Kurt I. and Ulijn, Rein V. ORCID logoORCID: https://orcid.org/0000-0001-7974-3779;
CORE (COnnecting REpositories)