On the Cellular Uptake and Exocytosis of Carbon Dots─Significant Cell Type Dependence and Effects of Cell Division.

Understanding the cellular uptake and exocytosis processes of nanoparticles (NPs) is essential for developing the nanomedicines and assessing the health risk of nanomaterials. Considerable efforts have been made to reveal how physicochemical properties of NPs influence these processes. However, little attention has been paid to how cell type impacts these processes, especially exocytosis. Herein, the uptake and exocytosis of the carbon dots (CDs) obtained from the carbonization of citric acid with polyethylenimine (PEI) oligomers (CDs-PEI) in five human cell lines (HeLa, A549, BEAS-2B, A431, and MDA-MB-468) are analyzed to understand how cell type influences the fate of CDs in cells. The cell division is taken into account by the correction of cell number for accurate quantification of the uptake and exocytosis of CDs-PEI. The results indicate that the cell type significantly affects the cellular uptake, trafficking, and exocytosis of CDs-PEI. Among the cell types investigated, MDA-MB-468 cells have the greatest capacity for both uptake and exocytosis, and HeLa cells have the least capacity. The kinetics of the exocytosis largely follows a single exponential decay function, with the remaining CDs-PEI in cells reaching plateaus within 24 h. The kinetic parameters are cell-dependent but insensitive to the initial intracellular CDs-PEI content. Generally, the Golgi apparatus pathways are more important in exocytosis than the lysosomal pathway, and the locations of CDs-PEI in the beginning of exocytosis are not correlated with their exocytosis pathways. The findings on the cell type-dependent cellular uptake and exocytosis reported here may be valuable to the future design of high-performance and safe CDs and related nanomaterials in general.