Shuming Nie and colleagues at Emory University and the Georgia Institute of Technology modified the quantum dots to increase their stability in vivo. By adding a multilayered shell to the exterior of CdSe/ZnS quantum dots, they increased the photostability of the dots, even when exposed to various in vivo environments, and simultaneously made them amenable to binding affinity ligands, such as antibodies, peptides, small-molecule drugs, or molecular inhibitors (Nature Biotechnology 22, 969-76; 2004).
To test the encapsulated dots, the team labeled them with an antibody that recognizes a protein expressed on prostate tumor cells called prostate-specific membrane antigen (PSMA). They then injected the dots into mice that carried human prostate tumors. Nie's group found that the dots concentrated in the tumor site in an antibody-dependent manner. They also found, as expected, that the quantum dots injected into the flank of an animal had higher fluorescence intensity than the same number of protein molecules labeled with green fluorescent protein.
Meanwhile, Sanford Simon and colleagues at Rockefeller University in New York have developed a new method using quantum dots that allows them to see injected tumor cells enter mouse lung tissue — their primary destination from a tail vein injection — in just 30 minutes. Previously, researchers had to wait weeks to determine if any of the injected cancer cells gave rise to metastases (Nature Medicine, September 2004, in press).
In order for tumor cells injected into the vein to form new metastases, they must pass through the bloodstream, attach to the endothelial lining of the vein, and move into the tissue, where they can form a nodule. Most cells don't survive the process. The first task was to check if the quantum dots put the tumor cells at an additional disadvantage in this highly stressful environment. The results were clear: "There was no adverse effect of quantum dots," Simon says.
The color of light emitted by quantum dots is determined by their size, making them, in effect, tunable to different wavelengths. Simon's group used this trait to investigate which step in metastasis limits where different tumors form. They labeled various tumor cell types with differently sized quantum dots, which show up as different colors, and then injected the mixture into the tail vein. All moved through the blood and attached to the endothelium with equal efficiency, but once in the tissue, only some types are able to survive and produce a new tumor. This suggests that something in the host tissue site determines which tumor cells can metastasize to a particular site.
Thus between the tunability and the strong fluorescence of quantum dots, researchers have been able to watch tumor formation in a way that was previously impossible.
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