Multivalent ligand−receptor interactions are critical to the function of membrane-enveloped biological and biomimetic nanoparticles, yet resulting nanoparticle shape changes are rarely investigated. Using the localized surface plasmon resonance (LSPR) sensing technique, we tracked the attachment of biotinylated, sub-100 nm lipid vesicles to a streptavidin-functionalized supported lipid bilayer (SLB) and developed an analytical model to extract quantitative details about the vesicle−SLB contact region. The experimental results were supported by theoretical analyses of biotin−streptavidin complex formation and corresponding structural and energetic aspects of vesicle deformation. Our findings reveal how varying the surface densities of streptavidin receptors in the SLB and biotin ligands in the vesicles affects the extent of nanometer-scale vesicle deformation. We also identify conditions, i.e., a critical ligand density, at which appreciable vesicle deformation began, which provides insight into how the membrane bending energy partially counterposes the multivalent binding interaction energy. These findings are generalizable to various multivalent ligand−receptor systems.
Lipid-based nanoparticles have emerged as a clinically viable platform technology to deliver nucleic acids for a wide range of healthcare applications. Within this scope, one of the most exciting areas of recent progress and future innovation potential lies in the material science of lipid-based nanoparticles, both to refine existing nanoparticle strategies and to develop new ones. Herein, the latest efforts to develop next-generation lipid-based nanoparticles are covered by taking a nanoarchitectonics perspective and the design, nucleic acid encapsulation methods, scalable production, and application prospects are critically analyzed for three classes of lipid-based nanoparticles: 1) traditional lipid nanoparticles (LNPs); 2) lipoplexes; and 3) bicelles. Particular focus is placed on rationalizing how molecular self-assembly principles enable advanced functionalities along with comparing and contrasting the different nanoarchitectures. The current development status of each class of lipid-based nanoparticle is also evaluated and possible future directions in terms of overcoming clinical translation challenges and realizing new application opportunities are suggested.
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