In Vivo Targeting of Hydrogen Peroxide by Activatable Cell-Penetrating Peptides

[Image: see text] A hydrogen peroxide (H(2)O(2))-activated cell-penetrating peptide was developed through incorporation of a boronic acid-containing cleavable linker between polycationic cell-penetrating peptide and polyanionic fragments. Fluorescence labeling of the two ends of the molecule enabled monitoring its reaction with H(2)O(2) through release of the highly adhesive cell-penetrating peptide and disruption of fluorescence resonance energy transfer. The H(2)O(2) sensor selectively reacts with endogenous H(2)O(2) in cell culture to monitor the oxidative burst of promyelocytes and in vivo to image lung inflammation. Targeting H(2)O(2) has potential applications in imaging and therapy of diseases related to oxidative stress.