Fate of CdSe/ZnS quantum dots in cells: Endocytosis, translocation and exocytosis.

Semiconductor quantum dots (QDs) have been extensively explored for extensive bioapplications, yet their cellular fate, especially exocytosis, has not been thoroughly investigated. Herein, we systematically investigated the whole cellular process from the endocytosis, intercellular trafficking, to the exocytosis of a typical QD, core/shell CdSe/ZnS QD. Using confocal laser scanning microscopy and flow cytometry, and after carefully eliminating the effect of cell division, we found that the QDs were internalized by HeLa cells with a time-, dose-, and serum-dependent manner. The cellular uptake was inhibited by serum, but eventually peaked after 4-6 h incubation with or without serum. The primary endocytosis pathway was clathrin-mediated, and actin- and microtubule-dependent in the medium with serum, while the caveolae-mediated endocytosis and macropinocytosis were more important for the QDs in the serum-free medium. Inside cells, most QDs distributed in lysosomes, and some entered mitochondria, endoplasmic reticulum, and Golgi apparatus. The translocation of the QDs from other organelles to Golgi apparatus was observed. The exocytosis of QDs was faster than the endocytosis, reaching the maximum in about one hour after cultured in fresh culture medium, with around 60% of the internalized QDs remained undischarged. The exocytosis process was energy- and actin-dependent, and the lysosome exocytosis and endoplasmic reticulum/Golgi pathway were the main routes. This study provides a full picture of behavior and fate of QDs in cells, which may facilitate the design of ideal QDs applied in biomedical and other fields.