A reversible fluorescence probe enables bioimaging and toxicity evaluation of lithium ion in living human cells.

The extensive use of lithium (Li) in green energy generation and storage poses a growing risk of human Li exposure. Therefore, advancing bioimaging and safety evaluation approaches for Li is crucial. This study introduces a new stratagem to reveal the toxicity effects of Li by developing a reversible lithium-sensitive probe (LSP). This probe, designed by conjugating spiropyran and azacrown ethers, enables highly selective imaging of Li within living cells at environmentally relevant concentrations, both extracellularly and in vitro. Utilizing this advanced probe, we conducted noninvasive monitoring to observe Li permeation through Aquaporin-1 (AQP1) channels in human embryonic kidney cells (HEK293) and its subsequent accumulation in the mitochondria. This mitochondrial accumulation led to decreased mitochondrial membrane potential, increased Cytochrome C (Cyto C) release, disruption of mitochondrial respiratory chain complex activity, and heightened cellular oxidative stress. These findings underscore LSP's utility in delineating spatial distributions and concentrations of Li in biological systems and monitor the Li-involved nephrotoxicity caused by mitochondrial damage.