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.