Light-Activated Anticancer Drug Targeted to DNA

One of the most successful chemotherapy agents against cancer is cisplatin because it binds to cancerous DNA and interrupts its repair process. However, it also destroys healthy tissue. Many scientists are trying to create alternative drugs or cisplatin analogs in attempts to find treatments without harmful side effects. One such approach to analog development is light-activated drugs, or photodynamic therapy (PDT).

A chemistry-biology research team from Virginia Polytechnic Institute and State University (Virginia Tech; Blacksburg, VA, USA) that has been researching both non-cisplatin drugs and cisplatin analogs has now combined its findings to create a molecular complex (supramolecule) that exploits cisplatin's tumor-targeting to produce a light-activated drug.

The latest findings from the team's research to create a DNA targeting, light-activated anticancer drug were presented at the 231st American Chemical Society meeting in Atlanta (GA, USA) in March 2006.

Chemistry professor Dr. Karen J. Brewer reported that the group has developed supramolecular complexes that combine light-absorbing PDT agents and cisplatin-like units. Earlier anticancer molecules created by the group have contained platinum-based molecules that bind to DNA. They have also developed new light-activated systems that are able to photocleave DNA. This research combines these two ways to target the drug to DNA using cisplatin-like units, directing the light activation to tumor cells and the subcellular target, DNA.

"In the past, our light-activated systems had to find the DNA within the cell, an often inefficient process. Now we have added the DNA-targeting drug,” Dr. Brewer said. "We were working on cisplatin analogs before, so we have tied it to light-activated systems.”

Cisplatin initiates its interaction with cancerous DNA by attaching to the nitrogen atoms of the DNA bases, normally guanine. The new supramolecules use this nitrogen-binding site to hold the light-activated drug at the target until signaled to activate. Thus, the new supramolecules can be delivered to the tumor site but remain inert until activated by a light signal. Light waves in the therapeutic range--that is, those that can penetrate tissue-- are used to activate these new drugs. The researchers are also attaching other molecules that emit ultraviolet (UV) light to track the movement of these compounds within cells.



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