Tethering functionality to lipid interfaces by a fast, simple and controllable post synthesis method

Abstract Hypothesis Liposomes require careful control of the surface design to ensure colloidal stability in complex matrices and target-specific binding to desired receptor units. Ideally, surface functionalization should be smart and controllable in terms of composition which is seldomly achieved by conventional methods. Therefore, a new strategy (insertion method) was developed and compared to the standard method (modification post-synthesis) using the model receptor biotin. Experiments Dipalmitoylphosphatidylethanolamine-biotin (DPPE-biotin) was used in both procedures, lipopeptide-biotin and cholesterol-biotin were tested additionally for insertion into the intact lipid bilayer. The insertion method was optimized regarding incubation time, temperature and vesicle stability. The biotinylated vesicles of both functionalization methods were characterized with respect to their size, ζ-potential and binding functionality. Findings Standard incorporation resulted in large variations in insertion-efficiency, high batch-to-batch differences, and an incorporation limit of 4 mol%. Best results were obtained through effortless insertion of the lipopeptide-biotin at room temperature. The concentration-controlled functionalization of liposomes (up to 10 mol%) could easily be monitored by the ζ-potential, resulted in reliable, quantitative binding to streptavidin and did not affect the analytical properties of the nanomaterial. This offers the possibility for a general modification strategy for lipid-based nanomaterials ideal for assay optimizations or multi-analyte detection.