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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 415-424 |
| Number of pages | 10 |
| Journal | Nature chemical biology |
| Volume | 13 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2017 |
Fingerprint
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Selective in vivo metabolic cell-labeling-mediated cancer targeting. / Wang, Hua; Wang, Ruibo; Cai, Kaimin; He, Hua; Liu, Yang; Yen, Jonathan; Wang, Zhiyu; Xu, Ming; Sun, Yiwen; Zhou, Xin; Yin, Qian; Tang, Li; Dobrucki, Iwona T.; Dobrucki, Lawrence W.; Chaney, Eric J.; Boppart, Stephen A.; Fan, Timothy M.; Lezmi, Stéphane; Chen, Xuesi; Yin, Lichen; Cheng, Jianjun.
In: Nature chemical biology, Vol. 13, No. 4, 01.04.2017, p. 415-424.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Selective in vivo metabolic cell-labeling-mediated cancer targeting
AU - Wang, Hua
AU - Wang, Ruibo
AU - Cai, Kaimin
AU - He, Hua
AU - Liu, Yang
AU - Yen, Jonathan
AU - Wang, Zhiyu
AU - Xu, Ming
AU - Sun, Yiwen
AU - Zhou, Xin
AU - Yin, Qian
AU - Tang, Li
AU - Dobrucki, Iwona T.
AU - Dobrucki, Lawrence W.
AU - Chaney, Eric J.
AU - Boppart, Stephen A.
AU - Fan, Timothy M.
AU - Lezmi, Stéphane
AU - Chen, Xuesi
AU - Yin, Lichen
AU - Cheng, Jianjun
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85012247636&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85012247636&partnerID=8YFLogxK
U2 - 10.1038/nchembio.2297
DO - 10.1038/nchembio.2297
M3 - Article
C2 - 28192414
AN - SCOPUS:85012247636
VL - 13
SP - 415
EP - 424
JO - Nature Chemical Biology
JF - Nature Chemical Biology
SN - 1552-4450
IS - 4
ER -