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Angew Chem Int Ed Engl. 2016 Apr 25;55(18):5452-6. doi: 10.1002/anie.201509601. Epub 2016 Mar 24.

Targeted Ultrasound-Assisted Cancer-Selective Chemical Labeling and Subsequent Cancer Imaging using Click Chemistry.

Author information

1
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, USA.
2
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
3
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. wdo@uiuc.edu.
4
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, USA. jianjunc@illinois.edu.

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.

KEYWORDS:

cell labeling; click chemistry; drug design; sugars; ultrasound

PMID:
27010510
PMCID:
PMC4918225
DOI:
10.1002/anie.201509601
[Indexed for MEDLINE]
Free PMC Article

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