Headgroup-Inversed Liposomes: Biointerfaces, Supported Bilayers and Applications.

Phospholipids are a major component of the cell membrane. In most natural phospholipids, the phosphate acts as a bridge, connecting the other portion of the polar headgroup with the hydrophobic tails. Such bridging phosphate is chemically quite inert. Synthetic lipids inversing the headgroup polarity of phosphocholine (PC) have been recently reported, and these are named CP lipids with a terminal phosphate, or CPe with the terminal phosphate capped by an ethyl group. This Feature Article summarizes the properties and applications of such inversed lipids. First, CPe liposomes were found to be highly resistant to protein adsorption with an even longer blood circulation time than PC liposomes, allowing for enhanced accumulation in tumor sites. CPe liposomes do not interact with PC liposomes either, and this observation was different from that reported using CP polymers, which adhere strongly to cells. Second, CP liposomes interact strongly with many metal oxide nanoparticles (but not silica) forming supported lipid bilayers, while PC liposomes only form supported bilayers on silica. Finally, CP liposomes are good metal ligands based on their exposed terminal phosphate. Zn2+ binds to CP liposomes so strongly that Zn2+ sandwiched multilayered lipid structures were observed. Aside from these fundamental aspects, the potential applications of these headgroup-inversed lipids in drug delivery and biosensor development have also been described, which in turn has promoted fundamental biointerface insights.