问题描述：
To meet the criteria for efficient delivery,the cationic amphiphile system condenses the reporter-DNA by displacement of the positively charged(inorganic)counterions and,after binding,'transports'the so-formed lipoplex to the cell surface.During these stages,DNA protection and preservation of the lipoplex morphology are important issues.After reaching the cell surface,interaction of the positively charged lipoplex with the negatively charged plasma membrane of the cell is facilitated,initiating the membrane transfer processes.The subsequent passage across the cell membrane and escape of the DNA materail into the cytoplasm finalize the first part of this trajectory.Endocytosis positively influences this part of the sequence,which involves the release of DNA from the endosomal compartment,facilitated by an as yet largely unresolved mechanism of disruption of the endosomal membrane.stages in the pathway clearly benefit from radically different types of morphological behavior of the lipoplex and the constituting lipids.
A potential method of improving the delivery capabilities of synthetic bilayer-forming amphiphiles is to induce a morphological change of the lipoplex from a relative stable lamellar phase(DNA condensing morphology)into an inverted hexagonal phase(H11),recognized as the most effective morphology for in vitro transfection.The hexagonal phase morphology does not necessarily facilitate the interaction with the cell membrane but appears pivotal for the escape from the endosomal compartment.Preferably,the morphological changes are only induced in the proximity of or after contact with the cell membrane or,alternatively,at the endosomal level.This rational has been applied to the design of novel cytofectins,the so-called Sunfish amphiphiles(Scheme 1),by attaching a flexible"antenna"to the cationic headgroup rather than a methyl moiety,as in the structurally related SAINT amphiphiles 2.
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A potential method of improving the delivery capabilities of synthetic bilayer-forming amphiphiles is to induce a morphological change of the lipoplex from a relative stable lamellar phase(DNA condensing morphology)into an inverted hexagonal phase(H11),recognized as the most effective morphology for in vitro transfection.The hexagonal phase morphology does not necessarily facilitate the interaction with the cell membrane but appears pivotal for the escape from the endosomal compartment.Preferably,the morphological changes are only induced in the proximity of or after contact with the cell membrane or,alternatively,at the endosomal level.This rational has been applied to the design of novel cytofectins,the so-called Sunfish amphiphiles(Scheme 1),by attaching a flexible"antenna"to the cationic headgroup rather than a methyl moiety,as in the structurally related SAINT amphiphiles 2.
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