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Scorpion Venom 'Paint' Created

Researchers from Fred Hutchinson Cancer Research Center and collaborators in Seattle have developed a fluorescent bioconjugate that targets numerous tumor types with high resolution. The details of their study appeared July 15 (2007) in Cancer Research.

The researchers called their molecule "tumor paint," building it from chlorotoxin, a scorpion venom protein that is nontoxic in mammals and has been shown to target glioma cells, and Cy5.5, a molecule that emits fluorescent light without requiring enzymatic cleavage within the cell and with minimal light absorption by water or hemoglobin.

After administering an early version of tumor paint to mice, the researchers found that adding Cy5.5 to chlorotoxin improved its tumor-targeting ability. "The resolution of cancer foci from normal tissue under simulated operating conditions was exquisite," down to the level of a few hundred cells, they wrote.

The team tested this conjugate in mouse models of medulloblastoma, sarcoma, and prostate and intestinal cancer, and found that it worked well in elucidating each of these tumors for as long as 15 days after administration.

The researchers suspect the specific target of the chlorotoxin on the cell membrane may be matrix metalloproteinase-2 (MMP-2). They transfected cells that failed to bind to tumor paint with plasmids containing MMP-2 and found that this facilitated attraction. Microscopy showed that the tumor paint and the MMP-2 clustered within the transfected cells.

However, pull-down assays were unable to show a direct bond between MMP-2 and tumor paint, and other experiments were unable to show an enzymatic relationship between them.

Posted September 2007

Source: National Cancer Institute bulleting, July 24, 2007

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