g(m3)-ganglioside and 1-2-dioleoylphosphatidylserine

Membrane-wrapped nanoparticles represent a versatile platform for utilizing specific lipid-receptor interactions, such as siallyllactose-mediated binding of the ganglioside GM3 to Siglec1 (CD169), for targeting purposes. The membrane wrap around the nanoparticles not only serves as a matrix to incorporate GM3 as targeting moiety for antigen-presenting cells but also offers unique opportunities for constructing a biomimetic surface from lipids with potentially protein-repellent properties. We characterize nonspecific protein adsorption (corona formation) to membrane-wrapped nanoparticles with core diameters of approximately 35 and 80 nm and its effect on the GM3-mediated targeting efficacy as a function of surface charge through combined in vitro and in vivo studies. The stability and fate of the membrane wrap around the nanoparticles in a simulated biological fluid and after uptake in CD169-expressing antigen-presenting cells is experimentally tested. Finally, we demonstrate in hock immunization studies in mice that GM3-decorated membrane-wrapped nanoparticles achieve a selective enrichment in the peripheral regions of popliteal lymph nodes that contain high concentrations of CD169-expressing antigen-presenting cells.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Biomimetic Materials; Cell Line; Dendritic Cells; G(M3) Ganglioside; Gene Expression; HeLa Cells; Humans; Immunization; Liposomes; Lymph Nodes; Macrophages; Mice; Nanoparticles; Phosphatidylserines; Primary Cell Culture; Sialic Acid Binding Ig-like Lectin 1; Surface Properties; Virion