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.