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Theranostics 2014; 4(4):420-431. doi:10.7150/thno.7265 This issue Cite

Research Paper

Cell Labeling and Tracking Method without Distorted Signals by Phagocytosis of Macrophages

Sun-Woong Kang^1,#, Sangmin Lee^2,#, Jin Hee Na², Hwa In Yoon³, Dong-Eun Lee⁴, Heebeom Koo⁵, Yong Woo Cho³, Sun Hwa Kim², Seo Young Jeong⁶, Ick Chan Kwon^2,7, Kuiwon Choi^2,*, Kwangmeyung Kim^2,*✉

1. Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Daejeon, Republic of Korea
2. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea
3. Department of Chemical Engineering, Hanyang University, Ansan, Republic of Korea
4. Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeonbuk, Republic of Korea
5. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
6. Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul, Republic of Korea
7. KU-KIST School, Korea University, Seoul, Republic of Korea
# These authors contributed equally to this work as first authors.
* These authors contributed equally to this work as corresponding authors.

✉ Corresponding author: Dr. Kwangmeyung Kim, Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea; Tel: +82-2-958-5909; Fax: +82-2-958-5909; E-mail: kimre.kr More

Abstract

Cell labeling and tracking are important processes in understanding biologic mechanisms and the therapeutic effect of inoculated cells in vivo. Numerous attempts have been made to label and track inoculated cells in vivo; however, these methods have limitations as a result of their biological effects, including secondary phagocytosis of macrophages and genetic modification. Here, we investigated a new cell labeling and tracking strategy based on metabolic glycoengineering and bioorthogonal click chemistry. We first treated cells with tetra-acetylated N-azidoacetyl-D-mannosamine to generate unnatural sialic acids with azide groups on the surface of the target cells. The azide-labeled cells were then transplanted to mouse liver, and dibenzyl cyclooctyne-conjugated Cy5 (DBCO-Cy5) was intravenously injected into mice to chemically bind with the azide groups on the surface of the target cells in vivo for target cell visualization. Unnatural sialic acids with azide groups could be artificially induced on the surface of target cells by glycoengineering. We then tracked the azide groups on the surface of the cells by DBCO-Cy5 in vivo using bioorthogonal click chemistry. Importantly, labeling efficacy was enhanced and false signals by phagocytosis of macrophages were reduced. This strategy will be highly useful for cell labeling and tracking.

Keywords: cell labeling, cell tracking, metabolic glycoengineering, click chemistry, chemical reporter.

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