The focus of this study was to determine the effect of surface coatings on the cellular uptake of nanoparticles and their fate inside cells and tissue using correlative microscopy. The nanoparticle properties and cellular uptake, including unique identification of the composition, locations and distribution of nanoparticles in cells, were determined using multiple microscopy techniques. The effect of coatings on the properties of platinum nanoparticles and their uptake by BEAS cells was undertaken to determine their relationship to the expression of heme oxygenease (HO-1) enzyme. The 1.3M PVP platinum nanoparticles produced very fine and well dispersed nanoparticles that were observed in the lysosomes of the BEAS cells and the other nanoparticles studied were present in large agglomerates.

The effect of polyethylene glycol (PEG) coating on the circulation time, agglomeration and accumulation of gold nanoparticles in the liver of mice was studied. A new approach to measuring the PEG coating thickness using high resolution TEM and negative staining techniques was introduced. The amount and distribution of gold in sections of the liver was determined using darkfield reflected light microscopy. Image analysis was used to determine the size, number and area fraction of agglomerates in the sections. The three dimensional distribution of gold nanoparticles in a single cell of the liver was obtained using ion abrasion scanning electron microscopy. The uncoated gold nanoparticles were taken up almost immediately by the Kupffer cells while the PEG coated nanoparticles were taken up after 2 hours. The native gold was observed in large, tightly packed agglomerates in lysosomes inside the cells, while the PEG coated nanoparticles were observed lining the inner surfaces of the lysosomes. Differences in the agglomeration of the gold nanoparticles had not been previously observed.

The effect of surface charge on the fate of QDs ingested by daphnia magna (water fleas) was explored. PEGylated QDs were not taken up by the nonsecretory cells that line the gut, they were observed in the lumen and lysed cells. A methodology for analyzing the cellular uptake of nanoparticles after in vitro and in vivo testing using optical and electron microscopy techniques is included.