title: In vitro targeting of synthesized antibody-conjugated dendrimer nanoparticles.
abstract: This study reports the synthesis and in vitro biological properties of dendrimer-antibody conjugates. The polyamidoamine dendrimer platform was conjugated to fluorescein isothiocyanate as a means to analyze cell binding and internalization. Two different antibodies, 60bca and J591, which bind to CD14 and prostate-specific membrane antigen (PSMA), respectively, were used as model targeting molecules. The binding of the antibody-conjugated dendrimers to antigen-expressing cells was evaluated by flow cytometry, confocal microscopy, and a new two-photon-based optical fiber fluorescence detection system. The conjugates specifically bound to the antigen-expressing cells in a time- and dose-dependent fashion, with affinity similar to that of the free antibody. Confocal microscopic analysis suggested at least some cellular internalization of the dendrimer conjugate. Dendrimer-antibody conjugates are a suitable platform for targeted molecule delivery into antigen-expressing cells.
authors.affiliation: Center for Biologic Nanotechnology, 9220 MSRB III, University of Michigan Medical School, Ann Arbor, Michigan 48109-0648, USA.
authors.forename: Thommey P
authors.initials: TP
authors.lastname: Thomas
authors.forename: Anil K
authors.initials: AK
authors.lastname: Patri
authors.forename: Andrzej
authors.initials: A
authors.lastname: Myc
authors.forename: Mon Thiri
authors.initials: MT
authors.lastname: Myaing
authors.forename: Jing Yong
authors.initials: JY
authors.lastname: Ye
authors.forename: Theodore B
authors.initials: TB
authors.lastname: Norris
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D000941:Antigens / Q000737:chemistry; D000954:Antigens, Surface / Q000737:chemistry; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D019169:Jurkat Cells; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D036103:Nanotechnology / Q000379:methods*; D017785:Photons; D011485:Protein Binding; D012542:Scattering, Radiation; D013997:Time Factors
chemical_list: D000941:Antigens; D000954:Antigens, Surface; D018950:Lipopolysaccharide Receptors; D046911:Macromolecular Substances; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II