Increase in Dye:Dendrimer Ratio Decreases Cellular Uptake of Neutral Dendrimers in RAW Cells.

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-OG n (n = 3, 4+, 4avg) into RAW cells was significantly lower than G3-OG n (n = 1, 2). The uptake of G3-OG n (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.