Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Evaluation of intracellular uptake of cyclic RGD peptides in integrin αvβ3-expressing tumor cells

  • Soyoung Lee (Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University) ;
  • Young-Hwa Kim (Department of Nuclear Medicine, Seoul National University Hospital) ;
  • In Ho Song (Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Ji Young Choi (Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Hyewon Youn (Department of Nuclear Medicine, Seoul National University Hospital) ;
  • Byung Chul Lee (Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Sang Eun Kim (Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine)
  • Received : 2020.12.17
  • Accepted : 2020.12.29
  • Published : 2020.12.31
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Abstract

The cyclic Arg-Gly-Asp (cRGD) peptide is well-known as a binding molecule to the integrin αvβ3 receptor which is highly expressed on activated endothelial cells and new blood vessels in tumors. Although numerous results have been reported by the usage of cRGD peptide-based ligands for cancer diagnosis and therapy, the distinct mechanisms, and functions of cRGD-integrin binding to cancer cells are still being investigated. In this study, we evaluated the internalization efficacy of different types of cRGD peptides (monomer, dimer and tetramer form) in integrin αvβ3 overexpressing cancer cells. Western blot and flow cytometric analysis showed U87MG expresses highly integrin αvβ3, whereas CT-26 does not show integrin αvβ3 expression. Cytotoxicity assay indicated that all cRGD peptides (0-200 µM) had at least 70-80% of viability in U87MG cells. Fluorescence images showed cRGD dimer peptides have the highest cellular internalization compare to cRGD monomer and cRGD tetramer peptides. Additionally, transmission electron microscope results clearly visualized the endocytic internalization of integrin αvβ3 receptors and correlated with confocal microscopic results. These results support the rationale for the use of cRGD dimer peptides for imaging, diagnosis, or therapy of integrin αvβ3-rich glioblastoma.

Keywords

Acknowledgement

This study was funded by the Korean Research Foundation grant (NRF-2018M2A2B3A02071842).

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