Researchers developing new arsenal in war against cancer

December 13, 2002

Blacksburg, Va. -- In the battle against cancer, Virginia Tech researchers have developed a potential warhead to better kill cancer cells, a new missile to deliver the warhead more efficiently to the diseased areas, and a new detonation device once the warhead is in place.

In a cross-disciplinary effort, the researchers, using photodynamic therapy (PDT), have obtained results in three different areas that, used together, have the possibility of providing more efficient, less invasive, and more specific treatments for cancer and other diseases such as age-related macular-degeneration.

A long-term concept has held that one should be able to use light-activated compounds to kill diseased cells, said Karen Brewer, associate professor of chemistry. The researchers have developed new tri-metallic supra-molecules that can be positioned in exact parts of cancer cells and excited by a therapeutic wavelength at which light propagates efficiently through tissue. Only when the light hits the supra-molecules do they become toxic to the cancer cells.

The advantages are many. The non-surgical process avoids the debilitating side effects of normal chemotherapy. The system enables the scientists to place the supra-molecules at specific locations in cells and to deliver light activating the cancer-killing molecules directly at that spot in a strength that does not harm other tissue. "This allows much lower dosages of light to be effective, so we can use agents that are more aggressive and not get the side effects of chemotherapy," Brewer said.

Researchers Shawn Swavey and Alvin Holder, along with students Lee Williams and Nathan Toft, working in the Brewer laboratory, developed the new mixed-metal supra-molecular complexes (medicines) that Brewer and Brenda Winkel, professor of biology, have proven are capable of photo-cleaving DNA, a normal therapeutic target in cells. The complexes are novel molecules whose chemistry allows the researchers to append them to other units.

At present, physicians use a chemical that is exposed to light and activates oxygen in photodynamic therapy. In tumor cells, oxygen is depleted rapidly, so those treatments can run out of oxygen and not kill the entire tumor, which can return. Brewer's new systems don't need oxygen, and the researchers can change the wavelength of light used. "We can fine tune the compound for light-absorbing characteristics," Brewer said. "By using a lower energy, we can better penetrate the body."

Brian Storrie, professor of biochemistry, and research scientist Maria Teresa Tarrago-Trani of biochemistry have developed the "rocket" with which to deliver the cancer-killing agents to particular organelles, or parts, in the cancer cells. "We have used a polypeptide that binds to a cell surface receptor, and that molecule is over-expressed for certain cancers. We can deliver photosynthesizers to the cancer," Storrie said.

The delivery vehicle is a B-fragment of a class of toxins known as shiga toxins. The A fragment is toxic, but the B fragment is a non-toxic delivery system. Storrie developed a way to use the B fragment to deliver the photo-dynamic agents developed by Brewer into the cells. This enables the researchers to target certain kinds of cancer cells that have receptors for the B fragment and deliver the agent to the exact spot in the cell so the supra-molecule can attack that part. This allows for the destruction of many parts in the cancerous cells.

Ken Meissner, senior research scientist with the Optical Science and Engineering Research (OSER) Center at Virginia Tech is developing the "detonation device" for the supra-molecules, which are nontoxic until hit by light. His specialty is the delivery of light to the correct tissues and to the supra-molecules positioned to kill the cells. Meissner develops better ways to get the light to the tumor and to understand how light passes through tissue

Together, the three-part attack opens up huge new areas for fighting cancer. "We can attach the delivery vehicles, change the light we need, change the biological target in the cells, and design a molecule that reacts with that part," Brewer said. In other words, Brewer can develop different molecules for different areas of the cells, Storrie can develop ways to get those molecules to the right places in the cells, and Meissner can develop methods to deliver the light needed to begin the killing of cancer cells. Or, Meissner can develop a new light-delivery system to work in a certain area, and then Brewer can develop a molecule that will kill tumor cells when excited with this light, and Storrie can get the molecule there.

The possibilities are greatly expanded by the variety of supra-molecules and the interactive work of these researchers. This exciting work is in the early stages, but the researchers hope it will someday be the basis for important strides in the treatment of cancer and other diseases.

The research is being done within the OSER Photodynamics Mini-center, a joint effort between the Carilion Biomedical Institute and Virginia Tech. Research groups collaborating under the mini-center include researchers Brewer, Storrie, Meissner, and Winkel, and Yannis Besieris and Brad Davis of electrical and computer engineering, Sun Young Kim of biochemistry, and Ed Wojcik of biology, all of Virginia Tech
-end-
Researcher contact information:
Karen Brewer 540-231-6579, kbrewer@vt.edu, www.chem.vt.edu/chem-dept/brewer/brewer.html
Brian Storrie 540-231-6434, storrie@vt.edu, www.biochem.vt.edu/faculty/storrie.html
Ken Meissner 540-231-2512, cmeissne@vt.edu

PR CONTACT: Sally Harris 540-231-6759 slharris@vt.edu

Virginia Tech

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