title: Fliposomes: pH-triggered conformational flip of new trans-2-aminocyclohexanol-based amphiphiles causes instant cargo release in liposomes.
abstract: A new type of pH-sensitive liposomes (fliposomes) was designed based on the amphiphiles that are able to perform a pH-triggered conformational flip (flipids). This flip disrupts the liposome membrane and causes rapid release of the liposome cargo, specifically in response to lowered pH. The flipids (1) and (2) are equipped with a trans-2-aminocyclohexanol conformational switch. pH-sensitive fliposomes containing one or both of these flipids, as well as POPC and PEG ceramide, were constructed and characterized. These compositions were stable at 4°C and pH 7.4 for several months. Fliposomes loaded with ANTS/DPX performed an unusually quick content release within a few seconds at pH below 8.5 (in case of 2) and 6.0 (in case of 1). This difference in pH sensitivity demonstrates a potential for the custom design of flipids by variation of the amino group to target areas with specific pH values. The pH titration curves for the fliposome leakage parallel the curves for the acid-induced conformational flip of 1 and 2 studied by ¹H NMR. A plausible mechanism of pH sensitivity starts with an acid-triggered conformational flip of 1 or 2, which changes the molecular size and shape, shortens the lipid tails, and perturbs the liposome membrane, resulting in the content leakage.
authors: Department of Chemistry, College of the Pacific, University of the Pacific, Stockton, California, USA.
authors: Xin
authors: X
authors: Liu
authors: Yu
authors: Y
authors: Zheng
authors: Nataliya M
authors: NM
authors: Samoshina
authors: Andreas H
authors: AH
authors: Franz
authors: Xin
authors: X
authors: Guo
authors: Vyacheslav V
authors: VV
authors: Samoshin
mesh_terms: D003511:Cyclohexanols / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation
chemical_list: C516358:2-aminocyclohexanol; D003511:Cyclohexanols; D008081:Liposomes