Ruthenium(II) anthraquinone complexes as two-photon luminescent probes for cycling hypoxia imaging in vivo

Recently, cycling hypoxia, with cycles of hypoxia followed by reoxygenation, was found to induce the up-regulation of HIF-1 activity in tumor cells and reduce the success rate of radiotherapy or chemotherapy. Thus, the ability to visualize cycling hypoxia in cells and in vivo is of great significance. To address this critical need, we have developed ruthenium(II) anthraquinone complexes as reversible two-photon luminescent probes; these probes are well suited for selectively and dynamically monitoring cycling hypoxia in live cells. Moreover, the probes can conveniently visualize inner hypoxia in 3D multicellular tumor spheroids and detect repeated cycles of hypoxia-reoxygenation in living zebrafish via two-photon luminescent imaging. The present study provides a powerful luminescent imaging tool for dynamically sensing of cycling hypoxia in vivo.