Since a direct evaluation of endosome leakage in intact cells could not be easily monitored, we have capitalized on synthetic lipid vesicles with a lipid composition mimicking that of the late endosomal membrane. We observed a modest but significant fluorescent dye release in the presence of (R-X-R) 4 -PMO. Importantly, the release of the probe was strongly promoted at pH 5.5 that is the characteristic pH for late endosomes. Although preliminary, these studies do indicate that more active (R-X-R) 4 -PMO conjugates in this series destabilize more efficiently these lipid vesicles than less active ones.