title: Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity.
abstract: Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay.
authors.affiliation: CSIRO Manufacturing Flagship, Private Bag 10, Clayton, VIC 3169, Australia. xavier.mulet@csiro.au maggie.zhai@csiro.au.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhai
authors.forename: Judith A
authors.initials: JA
authors.lastname: Scoble
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: George
authors.initials: G
authors.lastname: Lovrecz
authors.forename: Lynne J
authors.initials: LJ
authors.lastname: Waddington
authors.forename: Nhiem
authors.initials: N
authors.lastname: Tran
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Muir
authors.forename: Gregory
authors.initials: G
authors.lastname: Coia
authors.forename: Nigel
authors.initials: N
authors.lastname: Kirby
authors.forename: Calum J
authors.initials: CJ
authors.lastname: Drummond
authors.forename: Xavier
authors.initials: X
authors.lastname: Mulet
mesh_terms: D020285:Cryoelectron Microscopy; D004337:Drug Carriers / Q000737:chemistry; D066246:ErbB Receptors / Q000737:chemistry*; D005233:Fatty Alcohols / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D008024:Ligands; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D050866:Liquid Crystals; D008301:Maleimides / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D012542:Scattering, Radiation; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014965:X-Rays
chemical_list: D004337:Drug Carriers; D005233:Fatty Alcohols; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; D008055:Lipids; D008081:Liposomes; D008301:Maleimides; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; C038089:1,2-distearoylphosphatidylethanolamine; C043592:maleimide; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol; C512478:EGFR protein, human; D066246:ErbB Receptors