title: Lipid-Mediated Targeting with Membrane-Wrapped Nanoparticles in the Presence of Corona Formation.
abstract: 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.
authors.affiliation: Department of Chemistry and The Photonics Center, Boston University , Boston, Massachusetts 02215, United States.
authors.forename: Fangda
authors.initials: F
authors.lastname: Xu
authors.forename: Michael
authors.initials: M
authors.lastname: Reiser
authors.affiliation: Department of Chemistry and The Photonics Center, Boston University , Boston, Massachusetts 02215, United States.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Yu
authors.forename: Suryaram
authors.initials: S
authors.lastname: Gummuluru
authors.forename: Lee
authors.initials: L
authors.lastname: Wetzler
authors.affiliation: Department of Chemistry and The Photonics Center, Boston University , Boston, Massachusetts 02215, United States.
authors.forename: Björn M
authors.initials: BM
authors.lastname: Reinhard
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005679:G(M3) Ganglioside / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D061251:Primary Cell Culture; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000235:genetics / Q000276:immunology; D013499:Surface Properties; D014771:Virion / Q000737:chemistry / Q000276:immunology
chemical_list: C476507:1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine; D005679:G(M3) Ganglioside; D008081:Liposomes; D010718:Phosphatidylserines; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; D015060:1,2-Dipalmitoylphosphatidylcholine; C042511:1,2-dioleoylphosphatidylserine
keywords: GM3; Siglec1; antigen-presenting cells; gangliosides; hyperspectral imaging; stealth nanoparticle; zwitterion