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Nat Chem Biol. 2017 Apr;13(4):415-424. doi: 10.1038/nchembio.2297. Epub 2017 Feb 13.

Selective in vivo metabolic cell-labeling-mediated cancer targeting.

Author information

1
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
2
Jiangsu Key Laboratory for Carbon-Based Functional Materials &Devices, Institute of Functional Nano &Soft Materials (FUNSOM), Soochow University, Jiangsu, China.
3
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
4
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, China.
5
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
6
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
7
Department of Internal Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
8
Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
9
Department of Pathobiology at College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
10
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Changchun, People's Republic of China.
11
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
12
Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
13
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Abstract

Distinguishing cancer cells from normal cells through surface receptors is vital for cancer diagnosis and targeted therapy. Metabolic glycoengineering of unnatural sugars provides a powerful tool to manually introduce chemical receptors onto the cell surface; however, cancer-selective labeling still remains a great challenge. Herein we report the design of sugars that can selectively label cancer cells both in vitro and in vivo. Specifically, we inhibit the cell-labeling activity of tetraacetyl-N-azidoacetylmannosamine (Ac4ManAz) by converting its anomeric acetyl group to a caged ether bond that can be selectively cleaved by cancer-overexpressed enzymes and thus enables the overexpression of azido groups on the surface of cancer cells. Histone deacetylase and cathepsin L-responsive acetylated azidomannosamine, one such enzymatically activatable Ac4ManAz analog developed, mediated cancer-selective labeling in vivo, which enhanced tumor accumulation of a dibenzocyclooctyne-doxorubicin conjugate via click chemistry and enabled targeted therapy against LS174T colon cancer, MDA-MB-231 triple-negative breast cancer and 4T1 metastatic breast cancer in mice.

PMID:
28192414
PMCID:
PMC5458775
DOI:
10.1038/nchembio.2297
[Indexed for MEDLINE]
Free PMC Article

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