title: Increase in Dye:Dendrimer Ratio Decreases Cellular Uptake of Neutral Dendrimers in RAW Cells.
abstract: Neutral generation 3 poly(amidoamine) dendrimers were labeled with Oregon Green 488 (G3-OGn) to obtain materials with controlled fluorophore:dendrimer ratios (n = 1-2), a mixture containing mostly 3 dyes per dendrimer, a mixture containing primarily 4 or more dyes per dendrimer (n= 4+), and a stochastic mixture (n= 4avg). The UV absorbance of the dye conjugates increased linearly as n increased and the fluorescence emission decreased linearly as n increased. Cellular uptake was studied in RAW cells and HEK 293A cells as a function of the fluorophore:dendrimer ratio (n). The cellular uptake of G3-OGn(n= 3, 4+, 4avg) into RAW cells was significantly lower than G3-OGn(n= 1, 2). The uptake of G3-OGn(n= 3, 4+, 4avg) into HEK 293A cells was not significantly different from G3-OG1. Thus, the fluorophore:dendrimer ratio was observed to change the extent of uptake in the macrophage uptake mechanism but not in the HEK 293A cell. This difference in endocytosis indicates the presence of a pathway in the macrophage that is sensitive to hydrophobicity of the particle.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, 1107 Carl A Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, Michigan 48109, United States.
authors.forename: Sriram
authors.initials: S
authors.lastname: Vaidyanathan
authors.affiliation: Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
authors.forename: Milan
authors.initials: M
authors.lastname: Kaushik
authors.affiliation: Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
authors.forename: Casey
authors.initials: C
authors.lastname: Dougherty
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, 9220 MSRB III, 1150 West Medical Center Drive, SPC 5648, Ann Arbor, Michigan 48109, United States.
authors.forename: Rahul
authors.initials: R
authors.lastname: Rattan
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, 9220 MSRB III, 1150 West Medical Center Drive, SPC 5648, Ann Arbor, Michigan 48109, United States; Division of Cardiovascular Medicine, Internal Medicine, University of Michigan, 1500 E Medical Center Drive, Ann Arbor, Michigan 48109, United States; Veterans Affairs Health System, 2215 Fuller Road, Ann Arbor, Michigan 48105, United States.
authors.forename: Sascha N
authors.initials: SN
authors.lastname: Goonewardena
authors.affiliation: Department of Biomedical Engineering, University of Michigan, 1107 Carl A Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, Michigan 48109, United States; Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States; Macromolecular Science and Engineering, University of Michigan, 3062C H.H. Dow Building, 2300 Hayward Street, Ann Arbor, Michigan 48109, United States.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Banaszak Holl
authors.affiliation: Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, Louisiana 70125, United States.
authors.forename: Janet
authors.initials: J
authors.lastname: Monano
authors.affiliation: Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, Louisiana 70125, United States.
authors.forename: Stassi
authors.initials: S
authors.lastname: DiMaggio
keywords: HPLC; PAMAM dendrimer; dye; fluorescence emission; mammalian cell