Dose dependent distribution and aggregation of gold nanoparticles within human lung adeno-carcinoma cells

In this work, we discuss the distribution, aggregation and cytotoxicity of different treatment doses, 0.01, 0.05, 0.1, 0.2 and 0.5 nM, of poly(allylamine hydrochloride) (PAH) coated gold nanoparticles (Au NPs) with a human lung adeno-carcinoma cell line - A549 cells. By taking colorful scattering images and employing chromatic analysis, the evolution of Au NPs during cellular endocytosis and their distribution were revealed. With the lower treatment doses, 0.01 and 0.05 nM, Au NPs were mostly endocytosed and then clustered as larger aggregates inside cells. When the treatment dose was increased to 0.1 or 0.2 nM, a number of Au NPs were stuck on the membrane and formed two scattering color bands, yellow for larger aggregates inside cells and green for individual NPs on the membrane. By comparing with the cells treated with 0.1 nM Au NPs and dynasore, we find that the PAH coated Au NPs were up-taken into cells via dynamin dependent endocytosis. For the 0.5 nM dose, different from the 0.1 and 0.2 nM, there are large numbers of Au NPs stuck on the membrane, and furthermore, owing to the periodic lamellipodial contraction with rearward actin polymerization on the membrane, these stuck Au NPs were moved to and accumulated on the top of cells. From scanning electron microscopy (SEM) images, we find that the number and density of the Au NPs stuck on the membrane increases with the increasing treatment dose. Dual-beam focus ion beam (DBFIB) images showed the 2D covering and 3D stacking of the aggregated Au NPs on the membrane and inside endocytic vesicles respectively. Cytotoxicity testing indicates that the stuck Au NPs on the membrane would efficiently impact the cell viability. This work highlights the importance of an overall distribution of Au NPs in the NPs-cell interactive system.