April 24, 2006
High-Throughput Gene Expression Yields Insights on Quantum Dot Effects
Quantum dots have rapidly become a widely used tool for tracking how cells interact with a wide variety of biomolecules and drugs, but potential toxicities have raised concern that these nanoscale luminescent markers could themselves be triggering cellular activity that might confound experiment results. But now, a research team led by Fanqing Frank Chen, Ph.D., at the Lawrence Berkeley National Laboratory and the University of California at San Francisco, has shown that even very high doses of cadmium selenide/zinc sulfide (CdSe/ZnS) quantum dots coated with poly(ethylene glycol) (PEG) induce negligible toxicity in cells.
Reporting their work in the journal Nano Letters, Chen and his colleagues used gene chips to conduct high-throughput gene expression analysis on cells dosed with escalating amounts of both coated and uncoated CdSe/ZnS quantum dots. Using a gene chip with approximately 18,400 probes of known human genes, the investigators found that quantum dots coated with PEG induced changes in expression levels of approximately 50 genes, or about 0.2 percent of the genes surveyed. At least some of the affected genes code for proteins involved in endocytosis, a process that cells use to bring materials across the cell membrane, and intracellular trafficking processes that the cell would use to move such materials within the cell.
The researchers noted that overall, the cells’ response to doses of quantum dots as high as 80 nanomolar was negligible – typical exposure is likely 10 to 1,000 times less than the maximum dose used in this study. In particular, the researchers found no evidence that PEG-coated CdSe/ZnS quantum dots trigger expression of genes known to be turned on in response to either cadmium or selenium toxicity. The investigators also note that their experimental protocol should be useful for finding any long-term changes that result from either acute or chronic exposure to quantum dots.
This work is detailed in a paper titled, “Cellular effect of high doses of silica-coated quantum dot profiled with high throughput gene expression analysis and high content cellomics measurements.” Investigators from Affymetrix Inc., in Santa Clara, CA, and the University of California, Berkeley, also participated in this study. An abstract of this paper is available through PubMed.