@article{92178c43503a45029fcbfe2ef81543e5,
title = "Selective in vivo metabolic cell-labeling-mediated cancer targeting",
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 (Ac4 ManAz) 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 Ac4 ManAz 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.",
author = "Hua Wang and Ruibo Wang and Kaimin Cai and Hua He and Yang Liu and Jonathan Yen and Zhiyu Wang and Ming Xu and Yiwen Sun and Xin Zhou and Qian Yin and Li Tang and Dobrucki, {Iwona T.} and Dobrucki, {Lawrence W.} and Chaney, {Eric J.} and Boppart, {Stephen A.} and Fan, {Timothy M.} and St{\'e}phane Lezmi and Xuesi Chen and Lichen Yin and Jianjun Cheng",
note = "Funding Information: J.C. acknowledges support from the United States National Institute of Health (Director's New Innovator Award 1DP2OD007246), which partially supported the in vivo part of the research, and National Science Foundation (DMR 1309525), which partially supported the chemical design and synthesis of the work. L.Y. acknowledges the support from the National Natural Science Foundation of China (51403145 and 51573123), the Ministry of Science and Technology of China (2016YFA0201200), the Collaborative Innovation Center of Suzhou Nano Science and Technology, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). X.C. acknowledges the support from the National Natural Science Foundation of China (51528303). Research Fellowship. K.C. and Q.Y. acknowledge Beckman Institute Graduate Fellowship support at the University of Illinois at Urbana-Champaign. K.C., Q.Y., and L.T. acknowledge support from the NIH National Cancer Institute Alliance for Nanotechnology in Cancer Midwest Cancer Nanotechnology Training Center Grant R25 CA154015A. R.W. acknowledges the support of a CSTAR/T32 Fellowship through the NIH T32 Tissue Microenvironment Training Program. Publisher Copyright: {\textcopyright} 2017 Nature America, Inc., part of Springer Nature. All rights reserved.",
year = "2017",
month = apr,
day = "1",
doi = "10.1038/nchembio.2297",
language = "English (US)",
volume = "13",
pages = "415--424",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Nature Publishing Group",
number = "4",
}