In vivo stem cell tracking with imageable nanoparticles that bind bioorthogonal chemical receptors on the stem cell surface

Sangmin Lee, Hwa In Yoon, Jin Hee Na, Sangmin Jeon, Seungho Lim, Heebeom Koo, Sang Soo Han, Sun Woong Kang, Soon Jung Park, Sung Hwan Moon, Jae Hyung Park, Yong Woo Cho, Byung Soo Kim, Sang Kyoon Kim, Taekwan Lee, Dongkyu Kim, Seulki Lee, Martin G. Pomper, Ick Chan Kwon, Kwangmeyung Kim

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

It is urgently necessary to develop reliable non-invasive stem cell imaging technology for tracking the in vivo fate of transplanted stem cells in living subjects. Herein, we developed a simple and well controlled stem cell imaging method through a combination of metabolic glycoengineering and bioorthogonal copper-free click chemistry. Firstly, the exogenous chemical receptors containing azide (-N3) groups were generated on the surfaces of stem cells through metabolic glycoengineering using metabolic precursor, tetra-acetylated N-azidoacetyl-D-mannosamine(Ac4ManNAz). Next, bicyclo[6.1.0]nonyne-modified glycol chitosan nanoparticles (BCN-CNPs) were prepared as imageable nanoparticles to deliver different imaging agents. Cy5.5, iron oxide nanoparticles and gold nanoparticles were conjugated or encapsulated to BCN-CNPs for optical, MR and CT imaging, respectively. These imageable nanoparticles bound chemical receptors on the Ac4ManNAz-treated stem cell surface specifically via bioorthogonal copper-free click chemistry. Then they were rapidly taken up by the cell membrane turn-over mechanism resulting in higher endocytic capacity compared non-specific uptake of nanoparticles. During in vivo animal test, BCN-CNP-Cy5.5-labeled stem cells could be continuously tracked by non-invasive optical imaging over 15 days. Furthermore, BCN-CNP-IRON- and BCN-CNP-GOLD-labeled stem cells could be efficiently visualized using in vivo MR and CT imaging demonstrating utility of our stem cell labeling method using chemical receptors. These results conclude that our method based on metabolic glycoengineering and bioorthogonal copper-free click chemistry can stably label stem cells with diverse imageable nanoparticles representing great potential as new stem cell imaging technology.

Original languageEnglish
Pages (from-to)12-29
Number of pages18
JournalBiomaterials
Volume139
DOIs
Publication statusPublished - 2017 Sep

Keywords

  • Bioorthogonal copper-free click chemistry
  • Chemical receptors
  • Metabolic glycoengineering
  • Stem cell imaging
  • Unnatural sialic acids

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Lee, S., Yoon, H. I., Na, J. H., Jeon, S., Lim, S., Koo, H., Han, S. S., Kang, S. W., Park, S. J., Moon, S. H., Park, J. H., Cho, Y. W., Kim, B. S., Kim, S. K., Lee, T., Kim, D., Lee, S., Pomper, M. G., Kwon, I. C., & Kim, K. (2017). In vivo stem cell tracking with imageable nanoparticles that bind bioorthogonal chemical receptors on the stem cell surface. Biomaterials, 139, 12-29. https://doi.org/10.1016/j.biomaterials.2017.05.050