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

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. He...

Full description

Saved in:
Bibliographic Details
Published in:Biomaterials Vol. 98; pp. 192 - 202
Main Authors: Kalafatovic, Daniela, Nobis, Max, Son, Jiye, Anderson, Kurt I., Ulijn, Rein V.
Format: Journal Article
Language:English
Published: Netherlands Elsevier Ltd 01.08.2016
Subjects:
Advanced Basic Science
animal models
Animals
biocompatible materials
Biomaterials
Biomedical materials
Cancer therapy
Cell Line, Tumor
Cell Proliferation - drug effects
Dentistry
Doxorubicin
Doxorubicin - pharmacology
Doxorubicin - therapeutic use
Drug Carriers - chemistry
Enzymes
Humans
hydrolysis
Matrix Metalloproteinase 9 - metabolism
Mice, Nude
Micelles
MMP
Morphology transition
nanofibers
Nanofibers - chemistry
Nanofibers - ultrastructure
Nanostructure
Neoplasm Invasiveness
neoplasms
Neoplasms - drug therapy
Neoplasms - pathology
Peptides
Peptides - pharmacology
Self assembly
Surgical implants
tissues
Tumors
MMP
Self-assembly
Peptides
Morphology transition
Cancer therapy
ISSN:0142-9612, 1878-5905, 1878-5905
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0142-9612
1878-5905
1878-5905
DOI:10.1016/j.biomaterials.2016.04.039