Although quantum dots have unique properties that make them useful for biomedical applications, some can harm or kill cells. For instance, quantum dots often are made with cadmium, and excitation of these quantum dots could cause the release of highly toxic free Cd2+ ions inside cells.Therefore, researchers at McGill University in Montreal, at Humboldt Universität zu Berlin and at L’Université de Montréal studied the effect of cadmium-containing quantum dots on living cells. In particular, they exposed human breast cancer cells to CdTe and CdSe quantum dots, the latter having a ZnS shell. They capped the quantum dots with coordinating ligands to observe whether varying them altered cell viability.The investigators treated the cells with all of the quantum dots and used a common colorimetric assay to determine their effect on metabolic activity. They determined that CdTe quantum dots dramatically reduced metabolic activity after one hour. CdTe quantum dots capped with mercaptopropionic acid or cysteamine more strongly reduced metabolic activity than did those capped with N-acetylcysteine conjugated to cysteamine. The CdSe quantum dots only marginally decreased metabolic activity. After 24 hours, the CdTe quantum dots killed a significant amount of cells, whereas the CdSe quantum dots did not.The scientists employed a Zeiss confocal laser scanning microscope to examine the cells after exposure to CdTe quantum dots capped with mercaptopropionic acid or cysteamine, because the metabolic assay showed that they had the most toxic effect. These CdTe quantum dots caused the chromatin to aggregate and the nuclei to shrink and become deformed. The mitochondria enlarged and became more round, whereas the lysosomes became larger or fused together and congregated around the nucleus. A significant amount of the quantum dots were within lysosomes.To measure free cadmium ions, the researchers performed a fluorometric assay and employed a BMG Labtech plate reader to measure the fluorescence. CdSe quantum dots did not produce a detectable amount of free intracellular cadmium ions, but CdTe quantum dots yielded free intracellular cadmium ions ranging from 30 to 150 nM, depending on the capping molecule. CdTe quantum dots capped with cysteamine released more intracellular cadmium ions, but those capped with mercaptopropionic acid killed significantly more cells, even though they did not produce more free intracellular cadmium. Therefore, CdTe quantum dot-induced cell death did not depend only on the cadmium concentration. As a control, the researchers added CdCl2 to cells and established that free cadmium caused cell death in a manner dependent on the cadmium concentration. They concluded that CdTe quantum dots must kill cells via several mechanisms, including the release of free cadmium and other photooxidation processes dependent on their unique nanoparticulate properties. They also confirmed that CdSe quantum dots with a ZnS shell are relatively nontoxic, even after prolonged exposure.Langmuir, online publication, Jan. 13, 2007, doi: 10.1021/la060093j.