Headgroup-Inversed Liposomes: Biointerfaces, Supported Bilayers and Applications

Abstract

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. Zn binds to CP liposomes so strongly that Zn 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.

A pH‐Triggered Self‐Unpacking Capsule Containing Zwitterionic Hydrogel‐Coated MOF Nanoparticles for Efficient Oral Exendin‐4 Delivery

“…The MOF‐Gel nanoparticles containing MPDMSA residues had a slightly negative charge (Figure 1c), which supports the previously reported results. [ 42 ] Furthermore, by replacing the zwitterionic MPDMSA with a monomer containing a positively or negatively charged side group for the free‐radical copolymerization, various hydrogel‐coated MOF nanoparticles with positively or negatively charged surfaces (denoted as Ex@MIL101@Gel+ or Ex@MIL101@Gel−, respectively) were obtained (Figure 1c; Figure S3 and Scheme S1, Supporting Information). Because the surface charge of nanoparticles is a basic factor affecting their properties and functions, the alternating electrical properties of MOF‐Gel nanoparticles may be crucial in influencing their behaviors during intestinal transportation and absorption.…”

Modulating Noncovalent and Covalent Forces to Control Inverse Phosphocholine Lipid Self-Assembly on Inorganic Surfaces

“…26,27 The aforementioned efforts have relied on noncovalent strategies that result in weakly attached SLBs while there have also been creative strategies to fabricate SLB coatings on TiO2 surfaces by utilizing coordination chemistry-a line of research that not only has practical utility but also sheds light on the fundamental chemistry of phospholipid membranes on inorganic surfaces. 28 These strategies have been centered around inverse-PC lipids, which are structurally similar to PC lipids but have a flipped headgroup whereby the quaternary amine is connected to the glycerol backbone and the anionic phosphate group is presented outward. 29 The main example of an inverse-PC lipid is 2-((2,3-bis(oleoyloxy)propyl)dimethylammonio)ethyl hydrogen phosphate (DOCP) and negatively charged DOCP lipid vesicles have been reported to fuse with TiO2 nanoparticles to form SLB coatings.…”

Charge and Coordination Directed Liposome Fusion onto SiO2 and TiO2 Nanoparticles

“…Lipids with a phosphocholine (PC) headgroup are the main components of the eukaryotic cell membrane with excellent biocompatibility. For the majority of studies, silica (SiO 2 ) was used since PC liposomes can spontaneously fuse onto the silica surface (planar surfaces or nanoparticles) by a simple mixing at neutral or acid pH with salt. − Similar processes were observed also on mica and Al 2 O 3 -based surfaces, , although Ca 2+ was often used to facilitate liposome fusion. However, most other oxides, such as TiO 2 , do not form supported PC bilayers under physiological conditions. − …”