Cells Undergo Major Changes in the Quantity of Cytoplasmic Organelles after Uptake of Gold Nanoparticles with Biologically Relevant Surface Coatings

Here we use cryo soft X-ray tomography (cryo SXT), which delivers 3D ultrastructural volumes of intact cells without chemical fixation or staining, to gain insights about nanoparticle uptake for nanomedicine. We initially used dendritic polyglycerol sulfate (dPGS) with potential diagnostic and therapeutic applications in inflammation. Although dPGS coated gold nanoparticle (dPGS-AuNP) uptake followed a conventional endocytic/degradative pathway in human lung epithelial cell lines (A549), by cryo SXT we detected ~5% of dPGS-AuNP in the cytoplasm, a level undetectable by con-focal light microscopy. We also observed ~5% of dPGS-AuNP in a rarely identified sub-cellular site, namely lipid drop-lets, which are important for cellular energy metabolism. Finally, we also found substantial changes in the quantity of cytoplasmic organelles upon dPGS-AuNP uptake over the 1-6 h incubation period; the number of small vesicles and mitochondria significantly increased and the number of multivesicular bodies and the numbe...