A NIR iridium(III) complex-based reversible probe for assessing AD progression and screening anti-AD drugs through visualization of the “Cu2+-H2S seesaw” phenomenon in Alzheimer’s disease

The progression of Alzheimer’s disease (AD) is accompanied by the increase of copper ions (Cu2+) concentration and decrease of hydrogen sulfide (H2S) level in brain tissue, thus, reversible detection of Cu2+ and H2S is regarded as an important strategy for the diagnosis and intervention of AD. However, reliable tools for reversible tracking of Cu2+ and H2S and demonstrate their dynamic changes in AD are still lacking. Herein, this work developed a novel NIR Ir(III) complex-based probe, named NIR-Ir-DA, for reversible tracking of Cu2+ and H2S in AD cells and brain tissues. The newly prepared NIR luminescence probe exhibited fast response, high sensitivity and selectivity, good biocompatibility, which makes it to be used for reversible sensing of Cu2+ and H2S in multiple cycles in living cells and assessing AD progression in vitro and in vivo. Furthermore, using NIR-Ir-DA as a probe, we screened the theaflavin-3,3′-digallate (TF3) from polyphenols with an outstanding ability to reduce neuroinflammation, which would be greatly beneficial for AD therapy. These results indicated that NIR-Ir-DA could be a useful tool for understanding the role of “Cu2+-H2S seesaw” phenomenon in amyloid-β deposition, as well as for assessing AD progression and screening anti-AD drugs.