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ACS Nano. 2017 Oct 24;11(10):9825-9835. doi: 10.1021/acsnano.7b03150. Epub 2017 Sep 18.

In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides.

Author information

1
3Helix Inc , Salt Lake City, Utah 84117, United States.
2
Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112, United States
3
Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine , Salt Lake City, Utah 84132, United States.
4
MedImmune LLC , Gaithersburg, Maryland 20878, United States.
5
Division of Molecular Medicine & Genetics, Department of Internal Medicine, and the Life Sciences Institute, University of Michigan , Ann Arbor, Michigan 48109, United States.
6
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, United States

Abstract

Collagen, the major structural component of nearly all mammalian tissues, undergoes extensive proteolytic remodeling during developmental states and a variety of life-threatening diseases such as cancer, myocardial infarction, and fibrosis. While degraded collagen could be an important marker of tissue damage, it is difficult to detect and target using conventional tools. Here, we show that a designed peptide (collagen hybridizing peptide: CHP), which specifically hybridizes to the degraded, unfolded collagen chains, can be used to image degraded collagen and inform tissue remodeling activity in various tissues: labeled with 5-carboxyfluorescein and biotin, CHPs enabled direct localization and quantification of collagen degradation in isolated tissues within pathologic states ranging from osteoarthritis and myocardial infarction to glomerulonephritis and pulmonary fibrosis, as well as in normal tissues during developmental programs associated with embryonic bone formation and skin aging. The results indicate the general correlation between the level of collagen remodeling and the amount of denatured collagen in tissue and show that the CHP probes can be used across species and collagen types, providing a versatile tool for not only pathology and developmental biology research but also histology-based disease diagnosis, staging, and therapeutic screening. This study lays the foundation for further testing CHP as a targeting moiety for theranostic delivery in various animal models.

KEYWORDS:

bone formation; fibrosis; inflammation; matrix metalloproteinase; targeted delivery; triple helix

PMID:
28877431
PMCID:
PMC5656977
DOI:
10.1021/acsnano.7b03150
[Indexed for MEDLINE]
Free PMC Article

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