Selective in vivo metabolic cell-labeling-mediated cancer targeting
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 (Ac 4 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 Ac 4 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..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Nature chemical biology - 13(2017), 4, Seite 415 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Hua [VerfasserIn] |
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| Links: |
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| BKL: |
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| doi: |
10.1038/nchembio.2297 |
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| funding: |
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| 520 | |a 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 (Ac 4 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 Ac 4 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. | ||
| 700 | 1 | |a Wang, Ruibo |4 oth | |
| 700 | 1 | |a Cai, Kaimin |4 oth | |
| 700 | 1 | |a He, Hua |4 oth | |
| 700 | 1 | |a Liu, Yang |4 oth | |
| 700 | 1 | |a Yen, Jonathan |4 oth | |
| 700 | 1 | |a Wang, Zhiyu |4 oth | |
| 700 | 1 | |a Xu, Ming |4 oth | |
| 700 | 1 | |a Sun, Yiwen |4 oth | |
| 700 | 1 | |a Zhou, Xin |4 oth | |
| 700 | 1 | |a Yin, Qian |4 oth | |
| 700 | 1 | |a Tang, Li |4 oth | |
| 700 | 1 | |a Dobrucki, Iwona T |4 oth | |
| 700 | 1 | |a Dobrucki, Lawrence W |4 oth | |
| 700 | 1 | |a Chaney, Eric J |4 oth | |
| 700 | 1 | |a Boppart, Stephen A |4 oth | |
| 700 | 1 | |a Fan, Timothy M |4 oth | |
| 700 | 1 | |a Lezmi, Stéphane |4 oth | |
| 700 | 1 | |a Chen, Xuesi |4 oth | |
| 700 | 1 | |a Yin, Lichen |4 oth | |
| 700 | 1 | |a Cheng, Jianjun |4 oth | |
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