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Targeted Ultrasound‐Assisted Cancer‐Selective Chemical Labeling and Subsequent Cancer Imaging using Click Chemistry
Author(s) -
Wang Hua,
Gauthier Marianne,
Kelly Jamie R.,
Miller Rita J.,
Xu Ming,
O'Brien William D.,
Cheng Jianjun
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201509601
Subject(s) - click chemistry , in vivo , chemistry , cancer cell , microbubbles , reagent , cancer , ultrasound , biophysics , nanotechnology , cancer research , combinatorial chemistry , materials science , biology , medicine , microbiology and biotechnology , genetics , radiology
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 (Ac 4 ManAz) from microbubbles (MBs) and its metabolic expression in the cancer area. Ac 4 ManAz‐loaded MBs showed great stability under physiological conditions, but rapidly collapsed in the presence of tumor‐localized ultrasound pulses. The released Ac 4 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 Ac 4 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.