Highly Selective Artificial K⁺ Transporters Reverse Liver Fibrosis In Vivo

Liver fibrosis is a life-threatening disease that currently lacks clinically effective therapeutic agents. Given the close correlation between dysregulated intracellular K⁺ homeostasis and the progression of liver fibrosis, developing artificial K⁺ transporters mimicking the essential function of their natural counterparts in regulating intracellular K⁺ levels might offer an appealing yet unexplored treatment strategy. Here, we present an unconventional class of artificial K⁺ transporters involving the "motional" collaboration between two K⁺ transporter molecules. In particular, 6C6 exhibits an impressive EC₅₀ value of 0.28 μM (i.e., 0.28 mol % relative to lipid) toward K⁺ and an exceptionally high K⁺/Na⁺ selectivity of 15.5, representing one of the most selective artificial K⁺ transporters reported to date. Most importantly, our study demonstrates, for the first time, the potential therapeutic effect of K⁺-selective artificial ion transporters in reversing liver fibrosis both in vitro and in vivo.