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 (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.
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Ruibo
authors.identifier: 0000-0002-8753-7163
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Kaimin
authors.identifier: 0000-0001-9442-8312
authors.initials: K
authors.lastname: Cai
authors.affiliation: Jiangsu Key Laboratory for Carbon-Based Functional Materials &Devices, Institute of Functional Nano &Soft Materials (FUNSOM), Soochow University, Jiangsu, China.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yen
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Iwona T
authors.initials: IT
authors.lastname: Dobrucki
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Lawrence W
authors.identifier: 0000-0002-6807-217X
authors.initials: LW
authors.lastname: Dobrucki
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Chaney
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Department of Internal Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boppart
authors.affiliation: Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Fan
authors.affiliation: Department of Pathobiology at College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lezmi
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Changchun, People's Republic of China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory for Carbon-Based Functional Materials &Devices, Institute of Functional Nano &Soft Materials (FUNSOM), Soochow University, Jiangsu, China.
authors.forename: Lichen
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Jiangsu Key Laboratory for Carbon-Based Functional Materials &Devices, Institute of Functional Nano &Soft Materials (FUNSOM), Soochow University, Jiangsu, China.|Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.|Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D002241:Carbohydrates / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015335:Molecular Probes / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D058990:Molecular Targeted Therapy / Q000379:methods*; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D002241:Carbohydrates; D015335:Molecular Probes