Aggregate Formation of Oligonucleotides that Assist Molecular Imaging for Tracking of the Oxygen Status in Tumor Tissue.

Abstract

The use of DNA aggregates could be a promising strategy for the molecular imaging of biological functions. Herein, phosphorescent oligodeoxynucleotides were designed with the aim of visualizing oxygen fluctuation in tumor cells. DNA-ruthenium conjugates (DRCs) that consisted of oligodeoxynucleotides, a phosphorescent ruthenium complex, a pyrene unit for high oxygen responsiveness, and a nitroimidazole unit as a tumor-targeting unit were prepared. In general, oligonucleotides have low cell permeability because of their own negative charges; however, the DRC formed aggregates in aqueous solution due to the hydrophobic pyrene and nitroimidazole groups, and smoothly penetrated the cellular membrane to accumulate in tumor cells in a hypoxia-selective manner. The oxygen-dependent phosphorescence of DRC in cells was also observed. In vivo experiments revealed that aggregates of DRC accumulated in hypoxic tumor tissue that was transplanted into the left leg of mice, and showed that oxygen fluctuations in tumor tissue could be monitored by tracking of the phosphorescence emission of DRC.

• Authors: Kazuki Yoshihara, Kohei Takagi, Aoi Son, Ryohsuke Kurihara, Kazuhito Tanabe
• Journal: Chembiochem : a European journal of chemical biology (Chembiochem) Vol. 18 Issue 16 Pg. 1650-1658 (08 17 2017) ISSN: 1439-7633 [Electronic] Germany
• PMID: 28503897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Coordination Complexes
• Fluorescent Dyes
• Luminescent Agents
• Nitroimidazoles
• Oligodeoxyribonucleotides
• Oxazines
• Pyrenes
• Ruthenium
• nile red
• Oxygen

Topics

• A549 Cells
• Animals
• Coordination Complexes (chemical synthesis, chemistry, radiation effects)
• Fluorescent Dyes (chemistry)
• Humans
• Hydrogen-Ion Concentration
• Light
• Luminescent Agents (chemical synthesis, chemistry, radiation effects)
• Mice, Inbred BALB C
• Molecular Imaging
• Nitroimidazoles (chemical synthesis, chemistry)
• Oligodeoxyribonucleotides (chemical synthesis, chemistry, radiation effects)
• Oxazines (chemistry)
• Oxygen (analysis, chemistry)
• Pyrenes (chemical synthesis, chemistry)
• Ruthenium
• Tumor Hypoxia