In many ways, quantum dots are superior to typical fluorophores, but they cannot easily enter cells without chemical modification to their surface. Even if they enter cells, they may get stuck within cellular compartments. To address these issues, researchers at Emory University in Atlanta developed a chemical coating that enables quantum dots to enter cells and stay in the cytosol.In their experiments, they used conventional CdSe quantum dots coated with CdS and covered with a ZnS shell. They first coated the quantum dots with polyethylenimine, a polymer that enables the quantum dots to enter cells without causing major changes to their optical properties. However, the scientists found that uncoated polyethylenimine can harm cells and can aggregate under physiological conditions, so they added polyethylene glycol, which greatly reduced the cytotoxicity, prevented aggregation and kept the quantum dots in the cytosol, while polyethylenimine retained its ability to penetrate cells.The researchers verified that the quantum dots dispersed within the cytosol by using confocal fluorescence imaging with a PerkinElmer microscope and a Hamamatsu CCD camera. Employing the commonly used HeLa cells, they placed the quantum dots in the cellular medium and excited the semiconductor nanoparticles with 488-nm (visible) light.The location of the quantum dots varied with the number of polyethylene glycol groups. Semiconductor nanoparticles with two polyethylene glycol groups were in the cytosol, but those with four polyethylene glycol groups remained within cellular compartments. Colocalization with a dye commonly used to stain cellular compartments confirmed these results.The scientists determined whether polyethylene glycol reduced cytotoxicity by using a common cytotoxicity assay. The assay showed that two polyethylene glycol groups reduced cytotoxicity by more than 40 percent, and four polyethylene groups completely eliminated cytotoxicity, within experimental error. Although recent studies have shown that UV light can cause cadmium-containing quantum dots to release toxic free cadmium ions, the researchers believe that the cytotoxicity was caused by polyethylenimine because they used visible light. They reported their findings in the March 21 issue of the Journal of the American Chemical Society.In the future, they plan to modify the quantum dots to target specific molecules and to further improve the coating chemistry and probe design.