Currently, large doses of chemotherapy are required when treating certain forms of cancer, resulting in toxic side effects. The chemicals enter the body and work to destroy or shrink the tumor, but also harm vital organs and drastically affect bodily functions. Now, University of Missouri scientists have found a more efficient way of targeting prostate tumors by using gold nanoparticles and a compound found in tea leaves. This new treatment would require doses that are thousands of times smaller than chemotherapy and do not travel through the body inflicting damage to healthy areas.
The study is being published in the Proceedings of the National Academy of Science.
"In our study, we found that a special compound in tea was attracted to tumor cells in the prostate," said Kattesh Katti, curators' professor of radiology and physics in the School of Medicine and the College of Arts and Science and senior research scientist at the MU Research Reactor. "When we combined the tea compound with radioactive gold nanoparticles, the tea compound helped 'deliver' the nanoparticles to the site of the tumors and the nanoparticles destroyed the tumor cells very efficiently."
Currently, doctors treat prostate cancer by injecting hundreds of radioactive 'seeds' into the prostate. However, that treatment is not effective when treating an aggressive form of prostate cancer, said Cathy Cutler, research professor at the MU Research Reactor and co-author of the study. The size of the seeds and their inability to deliver effective doses hampers their ability to stop the aggressive form of prostate cancer.
In the study, the MU scientists created nanoparticles that are just the right size. Instead of hundreds of injections, the team only used one or two injections, and the nanoparticles were more likely to stay very close to the tumor sites.
Cutler and Katti have been working with colleagues Raghuraman Kannan, Anandhi Upendran, Charles Caldwell as well as others in the Department of Radiology and at the MU Research Reactor to develop and design the nanoparticles to the correct shape and size to treat prostate cancer. If the nanoparticles produced are too small, they can escape and spread; if they are made large enough, the nanoparticles will stay inside the tumor and treat it much more effectively than current methods.
"Current therapy for this disease is not effective in those patients who have aggressive prostate cancer tumors," Cutler said. "Most of the time, prostate cancers are slow-growing; the disease remains localized and it is easily managed. Aggressive forms of the disease spread to other parts of the body, and it is the second-leading cause of cancer deaths in U.S. men. However, we believe the gold nanoparticles could shrink the tumors, both those that are slow-growing and aggressive, or eliminate them completely."
"This treatment is successful due to the inherent properties of radioactive gold nanoparticles," Kannan said. "First, the gold nanoparticles should be made to the correct size, and second, they have very favorable radiochemical properties, including a very short half-life."
With a half-life of only 2.7 days, the radioactivity from the gold nanoparticles is finished within three weeks.
"Because of their size and the compound found in tea, the nanoparticles remain at the tumor sites," Upendran said. "This helps the nanoparticles maintain a high level of effectiveness, resulting in significant tumor volume reduction within 28 days of treatment."
In the current study, the team tested the nanoparticles on mice. Prior to human trials, the scientists will study the treatment in dogs with prostate cancer. Prostate cancer in dogs is extremely close to the human form of the disease.
"When it comes to drug discovery, MU is fortunate because we have a combination of experts in cancer research, animal modeling, isotope production and nanomedicine, and state-of-the-art research infrastructure to take discoveries from 'the bench to the bedside' and never leave campus," Katti said. "For example, we developed the nanoparticles here at our research reactor, which is one of the few places in the world that produces therapeutic, clinical grade radioisotopes. We then tested the radioactive gold nanoparticles in small animals in collaboration with other radiology researchers using testing facilities located at the Harry S. Truman Veterans Hospital. Our next steps include partnering with the College of Veterinary Medicine to treat larger animals with the hopes of having human clinical trials, held on our campus, soon."
Katti, Cutler, Kannan, Upendran and Caldwell were joined in the study by Ravi Shukla, Nripen Chanda and Ajit Zambre, all from the Department of Radiology.
- Ravi Shukla, Nripen Chanda, Ajit Zambre, Anandhi Upendran, Kavita Katti, Rajesh R. Kulkarni, Satish Kumar Nune, Stan W. Casteel, Charles Jeffrey Smith, Jatin Vimal, Evan Boote, J. David Robertson, Para Kan, Hendrik Engelbrecht, Lisa D. Watkinson, Terry L. Carmack, John R. Lever, Cathy S. Cutler, Charles Caldwell, Raghuraman Kannan, and Kattesh V. Katti. Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer. PNAS, July 16, 2012 DOI: 10.1073/pnas.1121174109
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