Enhancing functionalized liposome avidity to cells via lipid phase separation

Abstract

The addition of both cell-targeting moieties and polyethylene glycol (PEG) to nanoparticle (NP) drug delivery systems is a standard approach to improve the biodistribution, specificity, and uptake of therapeutic cargo. The spatial presentation of these molecules affects avidity of the NP to target cells in part through an interplay between the local ligand concentration and the steric hindrance imposed by PEG molecules. Here, we show that lipid phase separation in nanoparticles can modulate liposome avidity by changing the proximity of PEG and targeting protein molecules on a nanoparticle surface. Using lipid-anchored nickelnitrilotriacetic acid (Ni-NTA) as a model ligand, we demonstrate that the attachment of lipid anchored Ni-NTA and PEG molecules to distinct lipid domains in nanoparticles can enhance liposome binding to cancer cells by increasing ligand clustering and reducing steric hindrance. We then use this technique to enhance the binding of RGD-modified liposomes, which can bind to integrins overexpressed on many cancer cells. These results demonstrate the potential of lipid phase separation to modulate the spatial presentation of targeting and shielding molecules on nanocarriers, offering a powerful tool to enhance the efficacy of NP drug delivery systems.

Cell-free expression of Nipah virus transmembrane proteins for proteoliposome vaccine design

“…Further, nanoparticles containing hydrophobic bilayers are amenable to lipid adjuvants and antigens that can be colocalized with the other vaccine components (36)(37)(38)(39) and can accommodate multiple membrane proteins for the design of multivalent or universal vaccines. Finally, these scaffolds can be designed in a way that allows attached or integrated proteins to be spatially patterned (40). Taken together, using CFPS to decorate bilayerbased nanoparticles with viral membrane proteins is a promising strategy to create rapidly produced, low cost, and shelf-stable vaccines with the potential for enhanced potency relative to current strategies (Fig.…”

Simply and Cheaply Prepared Liposomal Membrane for Nanocarriers: High Encapsulation Efficiency Based on Broad Regulation of Surface Charges and pH-Switchable Performance

“…In addition, the liposome nanoparticles are prone to phase transition under external stimuli (such as high temperature, pH, enzyme, and external force field), which leads to reassembly and drug leakage. Traditional coating materials PEG 25 minimize the nonspecific interaction 26 in vivo, thus prolonging the circulation time. 27 However, it also markedly reduces their cellular uptake for immunogenicity and antigenicity, leading to a poor therapeutic effect.…”