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Novel light-sensitive compounds show promise for cancer therapy
Date:6/16/2009

ea for cancer therapy would be to embed the compounds in a matrix that you can place in the treatment site, then shine light on it to produce a high concentration of nitric oxide."

In designing the ruthenium nitrosyls, Rose and Mascharak were inspired by natural bacterial enzymes called nitrile hydratases, which release nitric oxide as a by-product when activated by light.

"We borrowed the idea from nature," Mascharak said. "Our initial goal was to understand these very unusual enzymes. Every hint that nature embedded in the behavior and structure of the enzyme we employed in designing a drug that can deliver nitric oxide in a very site-specific and controlled way."

Rose, who earned his Ph.D. this year, has been working on the project since 2004. He began by replacing the iron atom in a synthetic model of the enzyme with a different metal, ruthenium.

"Iron complexes are good in nature because they are highly reactive, but if you're trying to make a drug you want something that's more stable," Rose said. "The ruthenium complexes are much more stable when dissolved in water."

The first ruthenium nitrosyls he made released nitric oxide only under ultraviolet light, so Rose spent several years developing ways to sensitize them to specific wavelengths of visible light that could be used in photodynamic therapy. He did this by attaching dye molecules, called chromophores, to the ruthenium complex.

To test the resulting compounds as potential drugs, the chemists teamed up with breast cancer researcher Lindsay Hinck, a professor of molecular, cell, and developmental biology at UCSC. Hinck and postdoctoral researcher Rebecca Marlow worked with Rose to test the dye-sensitized ruthenium nitrosyls against breast cancer cells growing in tissue culture.

The unactivated compounds are fluorescent, which allowed the researchers to track them using a fluorescence microscope as the compounds were absorbed by the cancer
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Contact: Tim Stephens
stephens@ucsc.edu
831-459-2495
University of California - Santa Cruz
Source:Eurekalert

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