title: Targeted Ultrasound-Assisted Cancer-Selective Chemical Labeling and Subsequent Cancer Imaging using Click Chemistry.
abstract: Metabolic sugar labeling followed by the use of reagent-free click chemistry is an established technique for in vitro cell targeting. However, selective metabolic labeling of the target tissues in vivo remains a challenge to overcome, which has prohibited the use of this technique for targeted in vivo applications. Herein, we report the use of targeted ultrasound pulses to induce the release of tetraacetyl N-azidoacetylmannosamine (Ac4 ManAz) from microbubbles (MBs) and its metabolic expression in the cancer area. Ac4 ManAz-loaded MBs showed great stability under physiological conditions, but rapidly collapsed in the presence of tumor-localized ultrasound pulses. The released Ac4 ManAz from MBs was able to label 4T1 tumor cells with azido groups and significantly improved the tumor accumulation of dibenzocyclooctyne (DBCO)-Cy5 by subsequent click chemistry. We demonstrated for the first time that Ac4 ManAz-loaded MBs coupled with the use of targeted ultrasound could be a simple but powerful tool for in vivo cancer-selective labeling and targeted cancer therapies.
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors.forename: Marianne
authors.initials: M
authors.lastname: Gauthier
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors.forename: Jamie R
authors.initials: JR
authors.lastname: Kelly
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Miller
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. wdo@uiuc.edu.
authors.forename: William D
authors.initials: WD
authors.lastname: O'Brien
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, USA. jianjunc@illinois.edu.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001386:Azides / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism; D001940:Breast / Q000000981:diagnostic imaging / Q000378:metabolism; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D002232:Carbocyanines / Q000032:analysis; D045744:Cell Line, Tumor; D057930:Click Chemistry / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis; D006595:Hexosamines / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D061848:Optical Imaging / Q000379:methods; D016217:Ultrasonography, Mammary
chemical_list: D001386:Azides; D002232:Carbocyanines; D005456:Fluorescent Dyes; D006595:Hexosamines; C405953:N-azidoacetylmannosamine; C085321:cyanine dye 5
keywords: cell labeling; click chemistry; drug design; sugars; ultrasound