Virginia Tech group adds tools to DNA-targeted anti-cancer drugs

Chemistry and biology researchers at Virginia Tech have enhanced the abilities of the molecules they are creating to deliver killing blows to cancer cells. The man-made molecular complexes enter cancer cells and, when signaled, deliver killing medicine or cause the cell to change. The new supermolecules have more units that will absorb light – providing more control over the range of light frequencies that can be included and excluded as signals and the responses.

Karen Brewer, professor of chemistry, will give an invited talk, and her students will present a number of posters at the American Chemical Society (ACS) 230th annual meeting in Washington, D.C., Aug. 28 through Sept. 1 to explain their discoveries and applications.

Many scientists are racing to create ways to deliver cancer-killing drugs to tumors without harming surrounding tissue. At ACS meetings in August 2004 and March 2005, Brewer and her team announced the creation of molecular assemblies that solved two challenges facing photodynamic therapy, or activating drug delivery devices with light. The Brewer group’s systems could be activated by visible light in the therapeutic range – a wavelength not blocked or reflected by tissue. The systems also were able to operate without oxygen.

The group now has more kinds of supramolecular assemblies that absorb therapeutic light and they are adding units to the structure. For instance, they added platinum, a metal with anticancer activity because it binds to DNA inhibiting cell replication. “Using platinum assures that we are activating complexes that are already attached to the target,” Brewer said. “The previous systems had an association with DNA but could release, which might result in an impact on other parts of the cell.”

Because the therapeutic complexes only activate with visible light, the researchers are now able to add a luminescent tag that glows in the presence of ultra violet (UV) light. “The UV light does not activate the system but will allow us to see such things as how the assembly enters cells and how much of the drug reaches the DNA,” Brewer said. “It is a common practice in the medical field to use luminescent dyes to study cells, so pathology labs will have the equipment needed to monitor drug delivery.

Brewer is giving her invited talk, “Applications of mixed-metal supramolecular complexes in the development of chemotherapeutic and photodynamic therapy agents” (INOR 219), at 9:15 a.m. Monday Aug. 29, in room 145B of the Washington, D.C., Convention Center. She will talk about adding functionality to the group’s supramolecular assemblies.

Co-authors of the research are Matthew T. Mongelli, of Maywood, N.J., post doctoral associate in chemistry; Virginia Tech chemistry undergraduate students Jerita Dubash, of Ashburn, Va., and Matthew Jeletic, of Centreville, Va., graduate students David F. Zigler, of Sterling, Ill., Julie Heinecke, of Powhatan, Va., and Ran Miao, of Zhangzhou City, China, and biology professor Brenda S. J. Winkel.

In addition, members of the Virginia Tech group are presenting several posters related to the photodynamic therapy research.

Three posters will be available from 7 to 9 p.m. Sunday, Aug. 28. Dubash will present “Time dependent photochemical studies of Rh centered mixed-metal supramolecular complexes which photocleave DNA” (INOR 136), co-authored by Mongelli, Winkel, and Brewer. Heinecke will present “Using 31P NMR and a phosphine tag to monitor stereochemistry and reactivity of Ru(II) light absorbing units in supramolecular assemblies” (INOR 133), co-authored by Mongelli and Brewer. And Zigler will present “Luminescence tagging of 2,2’-bipyridine complexes of Fe(II): Synthesis and metal binding studies of 4-[N-(2-anthryl)amido]-4’-methyl-2,2’-bipyridine” (INOR 141), co-authored by graduate students Mark Elvington and Jared Brown and Brewer.

At the SciMix poster session from 8 to 10 p.m. Monday, Aug. 29, Mongelli will present “Tuning visible light initiated bioreactivity of mixed metal supramolecular complexes by subunit variation” (INOR 96), co-authored by Dubash, Jeletic, Winkel, and Brewer.

And from 7 to 9 p.m. Tuesday, Aug. 30, there will be two posters from the Brewer group. Miao will present “Dictating spatial organization of acceptor and donor orbitals in mixed-metal:mixed-ligand supramolecular complexes” (INOR 392), co-authored by Brewer. And Jeletic will present “Osmium(II) chromophores containing 2,2’:6’,2″-terpyridine and 2,3-bis(2-pyridyl)pyrazine and their use in the construction of supramolecular complexes” (INOR 385), co-authored by Mongelli and Brewer.

All of the poster sessions are in the Washington, D.C., Convention Center Hall A.

Brewer’s photodynamic therapy agent research has been funded by the National Science Foundation (CHE-0408445). Brewer’s group is working in collaboration with Theralase Technologies Inc., a medical laser company in Canada that holds the license on the patented systems.