Green Tea and Gold to Fight Prostate Cancer

Gold Nanoparticles Could Treat Prostate Cancer With Fewer Side Effects than Chemotherapy, MU Researchers Find

VIDEO: Gold Nanoparticles Could Treat Prostate Cancer With Fewer Side Effects than Chemotherapy

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COLUMBIA, Mo. – 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.

Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the 198Au ?-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible 198AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of 198AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable 198AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.

By coating radioactive gold nanoparticles with a green tea component, researchers of the University of Missouri have enhanced the delivery of the nanoparticles to tumors and their retention at the tumor site. In earlier work the researchers, led by Kattesh Katti and Cathy Cutler, showed us shrinkage of prostate cancer tumors in mice by using gold nanoparticles. However, they also found that a certain component in green tea, known as epigallocatechin-gallate (EGCg), was attracted to prostate tumor cells. By combining the nanoparticles with the tea component, the treatment will now be more efficient. The study results are published in the Proceedings of the National Academy of Sciences.

For the treatment, the size of a tumor is important in deciding whether surgical removal is an option. The smaller size can also have a positive influence on the success rate of chemotherapy and immunotherapy. In earlier research, the mice prostate tumors showed a 82% volume reduction and there were no side effects of the injected radioactive gold nanoparticles, also known as 198AuNP. The half-life of the nanoparticles is just 2.7 days and after three weeks there is no radioactivity anymore. The size of these small nanoparticles makes it possible to reach the tumor cells through the tumor vasculature, which often consist of small, fragile blood vessels.

The next step will be to acquire permission to perform clinical trials to test the effectiveness in human tumors. But before the clinical trials will start, the researchers will study the effect of the radioactive gold nanoparticles in dogs with prostate cancer.

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