Design of colipids with controlled lateral distance of head group moieties for targeting strategies in the field of lipid-based nanoparticles

Lipidoids with polyethylene glycol lateral spacers can integrate into liposome bilayers in a way that depends on both lipidoid structure and liposome composition, as measured by EPR.

• Why it matters: Targeted lipid nanoparticles rely on how ligand-bearing lipids present their binding motifs, yet lateral spacing between ligand units is largely unaddressed.
• What they did: The team synthesized lipidoids with a primary amine head group and a paramagnetic probe, then used continuous-wave EPR to quantify integration into model liposomes and DEER to track conformational changes.
• The result: EPR and DEER show that lipidoid structure and liposome composition govern bilayer association and induce conformational shifts upon integration, enabling design of lateral ligand spacing strategies.

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