Structure-Function Relationships of New Lipids Designed for DNA Transfection

摘要: Cationic liposome/DNA complexes can be used as nonviral vectors for direct delivery of DNA-based biopharmaceuticals to damaged cells and tissues. To obtain more effective safer liposome-based gene transfection systems, two cationic lipids with identical head groups but different chain structures are investigated respect their in vitro gene-transfer activity, cell-damaging characteristics, physicochemical properties. The activities the very different. Differential scanning calorimetry synchrotron small- wide-angle X-ray scattering give valuable structural insight. A subgel-like structure high packing density phase-transition temperature from gel liquid-crystalline state found lipid 7 (N′-2-[(2,6-diamino-1-oxohexyl)amino]ethyl-2,N-bis(hexadecyl)propanediamide) containing saturated chains. Additionally, an ordered head-group lattice based on formation a hydrogen-bond network is present. In contrast, 8 (N′-2-[(2,6-diamino-1-oxohexyl)amino]ethyl-2-hexadecyl-N-[(9Z)-octadec-9-enyl]propanediamide) one unsaturated shows lower reduced density. These properties enhance incorporation helper cholesterol needed transfection. Both lipids, either pure or mixtures cholesterol, form lamellar phases, which preserved after addition DNA. However, system separates into phases DNA without On increasing temperature, released only phase intercalated strands observed. conversion temperatures systems studied. important parameter seems charge membranes, result solubility membranes. Therefore, binding affinities achieved.