Iridium(III) Anthraquinone Complexes as Two‐Photon Phosphorescence Probes for Mitochondria Imaging and Tracking under Hypoxia

Abstract

In the present study, four mitochondria-specific and two-photon phosphorescence iridium(III) complexes, Ir1-Ir4, were developed for mitochondria imaging in hypoxic tumor cells. The iridium(III) complex has two anthraquinone groups that are hypoxia-sensitive moieties. The phosphorescence of the iridium(III) complex was quenched by the functions of the intramolecular quinone unit, and it was restored through two-electron bioreduction under hypoxia. When the probes were reduced by reductase to hydroquinone derivative products under hypoxia, a significant enhancement in phosphorescence intensity was observed under one- (λ=405 nm) and two-photon (λ=720 nm) excitation, with a two-photon absorption cross section of 76-153 GM at λ=720 nm. More importantly, these probes possessed excellent specificity for mitochondria, which allowed imaging and tracking of the mitochondrial morphological changes in a hypoxic environment over a long period of time. Moreover, the probes can visualize hypoxic mitochondria in 3D multicellular spheroids and living zebrafish through two-photon phosphorescence imaging.

Super‐Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore

“…Highly mobile and dynamic in living cells, mitochondria are the energy‐generating organelles of cells, the disorder of which is associated with various diseases, including Alzheimer's, Parkinson's, and cancer . Recently developed super‐resolution fluorescence microscopies such as stimulated emission deletion (STED), structured illumination microscopy (SIM), and stochastic optical reconstruction microscopy (STORM), as well as other single‐molecule super‐resolution imaging techniques, are enhanced new tools for investigating the dynamics of subcellular structures, including mitochondria.…”

Luminescent chemosensors by using cyclometalated iridium(iii) complexes and their applications

“…8–13 For example, their long-lived phosphorescence can allow them to be distinguished from an autofluorescent background, which is common in biological milieu, by the use of time-resolved emission spectroscopy (TRES). This method involves setting the time gate on the spectrophotometer to be greater than the fluorescence decay time of endogenous fluorophores, such that only long-lived phosphorescent signals are recorded.…”

Quinone-based fluorophores for imaging biological processes

“…The authors demonstrated the ability of compounds 54-57 to act as mitochondrial markers. 49 The phosphorescence of Ir(III) complexes was quenched by the quinoidal moiety, and restored under hypoxic conditions after a two-electron bioreduction process. The probes were activated by reductases in the presence of NADPH, which triggered the conversion of the anthraquinone moiety into the hydroquinone, rendering 26-fold increase in emission.…”