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

The use of DNA aggregates could be a promising strategy for molecular imaging of biological functions. Herein, phosphorescent oligodeoxynucleotides were designed with the aim of visualizing oxygen fluctuation in tumor cells. We prepared DNA-ruthenium conjugate (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. In general, oligonucleotides have low cell permeability because of their own negative charges; however, the present 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. We also observed the oxygen-dependent phosphorescence of DRC in cells. In vivo experiments revealed that aggregates of DRC accumulated in hypoxic tumor tissue that was transplanted in the left leg of mice, and showed that oxygen fluctuations in tumor tissue could be monitored by tracking of phosphorescence emission of DRC.