Coumarin Excimer Nanotube for Long-Time Lysosome Tracking

Lysosome abnormality closely relates to a variety of diseases; thus, its long-time tracking could benefit accurate disease diagnosis. Current long-time lysosome imaging probes are not biocompatible enough, while compatible peptide-based probes are easily degraded by the abundant proteinases in lysosome. Herein, we rationally design a d-amino acid-containing peptide Cys(StBu)-d-Glu-Lys(coumarin)-d-Glu-CBT (Cou-D/L-CBT) which is subjected to intracellular GSH-initiated CBT-Cys click reaction and assembles into nanotubes in acidic lysosome. <i>In vitro</i> experiments showed that, under reduction environment and at pH 4.8, Cou-D/L-CBT assembled into nanotubes with an outer diameter of 156 nm, accompanied by "turn-on" coumarin excimer fluorescence at 550 nm. Cell experiments indicated that while Cou-D/L-CBT provided 29 h of lysosome fluorescence imaging, control probe Cou-L-CBT sustained only 6 h. We expect that our Cou-D/L-CBT could be applied for <i>in vitro</i> sensitive diagnosis of lysosome-related diseases in the clinic in the near future.