A Ring-Flippable Sugar as a Stimuli-Responsive Component of Liposomes

For the development of a liposome that takes in and out a drug in response to stimuli, 2,4-diaminoxylose (Xyl), which allows stimuli-responsive conformational switches between C-4(1) and C-1(4), was incorporated into a lipid structure: Xyl derivatives with C8 and C16 methylene chains at the 1,3-positions (C8Xyl and C16Xyl) were synthesized. H-1 NMR spectroscopy indicates that the addition of Zn2+ and then H+ induces conformational switches from the chair (C-4(1)) to the reverse chair (1C4) and C-1(4)-to-C-4(1), respectively, at Xyl; this leads to transformation of the lipids between linear and bent structures. Osmotic pressure and electron microscopy studies demonstrate that C8Xyl in water forms spherical solid aggregates (C8Xyl +/- Zn), which are converted into liposomes (C8Xyl+ Zn) upon the addition of Zn2+, and C16Xyl forms liposomes regardless of the presence of Zn2+. The aggregates of C8Xyl + Zn incorporated a fluorophore and only C8Xyl+ Zn released the content upon the addition of HCl. This study shows that Xyl could be a stimuli-responsive component of a liposome.