A detailed analysis of silver nanoparticle (NP) uptake and trafficking in the murine macrophage cell line J774A.1 through spectral analysis of the resonance wavelength of the metal NP cargo is presented. The NP spectra reveal a strong phenotypic variability in the NP uptake and processing on the single cell level. Cells containing non- or low-agglomerated NPs are found to coexist with cells containing NPs of varying degrees of NP agglomeration, clearly indicated by a spectral red-shift in the resonance wavelength. Pharmacological inhibition studies indicate that the observed differences in the intracellular NP organization result from coexisting actin- and clathrin-dependent endocytosis mechanisms. Correlation with fluorescence macrophage maturity markers shows that differentiated J774A.1 macrophages preferentially contain compact NP agglomerates, whereas monocyte-like macrophages contain non-agglomerated NPs.

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