Site-Specific In Vivo Bioorthogonal Ligation via Chemical Modulation

Heebeom Koo; Jeong Heon Lee; Kai Bao; Yunshan Wu; Georges El Fakhri; Maged Henary; Seok Hyun Yun; Hak Soo Choi

doi:10.1002/adhm.201600574

Site-Specific In Vivo Bioorthogonal Ligation via Chemical Modulation

Adv Healthc Mater. 2016 Oct;5(19):2510-2516. doi: 10.1002/adhm.201600574. Epub 2016 Aug 29.

Authors

Heebeom Koo^{1

2}, Jeong Heon Lee³, Kai Bao³, Yunshan Wu⁴, Georges El Fakhri³, Maged Henary⁵, Seok Hyun Yun⁶, Hak Soo Choi⁷

Affiliations

¹ Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA.
² Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea.
³ Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
⁴ Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA.
⁵ Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA. mhenary1@gsu.edu.
⁶ Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA. syun@hms.harvard.edu.
⁷ Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. hchoi12@mgh.harvard.edu.

Abstract

A critical limitation of bioorthogonal click chemistry for in vivo applications has been its low reaction efficiency due to the pharmacokinetic barriers, such as blood distribution, circulation, and elimination in living organisms. To identify key factors that dominate the efficiency of click chemistry, here a rational design of near-infrared fluorophores containing tetrazine as a click moiety is proposed. Using trans-cyclooctene-modified cells in live mice, it is found that the in vivo click chemistry can be improved by subtle changes in lipophilicity and surface charges of intravenously administered moieties. By controlling pharmacokinetics, biodistribution, and clearance of click moieties, it is proved that the chemical structure dominates the fate of in vivo click ligation.

Keywords: click chemistry; near-infrared imaging; pharmacokinetics; real-time imaging; targeted contrast agent.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Click Chemistry / methods
Fluorescent Dyes / chemistry*
Ligation
Mice
Tissue Distribution

Substances

Fluorescent Dyes

Abstract

Publication types

MeSH terms

Substances

Grants and funding