News — Nanotechnology scientists at two Arkansas research institutions have developed a method of detecting, tracking, and killing cancer cells in real time with carbon nanotubes.

The discovery opens the prospect of a new, major front in the fight to eradicate cancer with promise for a new generation of cancer treatment beyond surgery, radiation, and chemotherapy.

Dr. Alex Biris, University of Arkansas at Little Rock (UALR) chief scientist at the Nanotechnology Center and assistant professor of applied science in University's Donaghey College of Engineering and Information Technology, and Dr. Vladimir P. Zharov, professor and director of the Phillips Classic Laser and Nanomedicine Laboratories in the University of Arkansas for Medical Sciences (UAMS) Winthrop P. Rockefeller Cancer Institute, published their findings in the latest issue of the Journal of Biomedical Optics.

"Until now, nobody has been able to fully understand and study in vivo and in real time how these nanoparticles travel through a living system," Biris said. "By using Raman spectroscopy, we showed that it is possible not only to monitor and detect nanomaterials moving through the circulation, but also to detect single cancer cells tagged with carbon nanotubes. In this way, we can measure their clearance rate and their biodistribution kinetics through the lymph and blood systems."

Zharov emphasized that in vivo Raman flow cytometry is promising for the detection and identification of a broad spectrum of various nanoparticles with strong Raman scattering properties, such as cells, bacteria, and even viruses.

"Before any clinical application of nanoparticles, it is imperative to determine their pharmacological profiles," Zharov said. "And this tool will provide this function as a supplement or even an alternative to the existing methods."

In their research, Biris, Zharov, and UAMS colleague Ekaterina Galanzha, M.D., injected a single human cancer cell containing carbon nanotube material in the tail vein of a test rat. They were able to follow the circulation of the carbon nanotubes in the blood vessels to the rat's ear, tracking the cell through the rat's blood stream, lymphatic system, and tissue with a Raman spectrometer.

In the same issue of the scientific journal, Biris and Zharov published a second paper discussing how nanoparticles can tag cancer cells. A laser then heats the nanoparticles, killing the cancer cell.

"If we are able to target cancer cells using these nanomaterials, we can monitor where the cancer cells are specifically located, and then we can kill them," Biris said.

He said the live rat experiment shows how the cancer killing process leaves only a dead cell and nanoparticles that, within a matter of hours, disintegrate and die.

Dr. Mary Good, dean of UALR's Donaghey College of Engineering and Information Technology, said the medical and economic ramifications of the discovery are significant.

"The research Dr. Biris and Dr. Zharov have conducted indeed is significant and promising," said Good, former technology undersecretary of Commerce in the Clinton administration. "It points to a whole new direction for medical applications for nanoparticles. There still is extensive time needed for research into the ultimate utility for these approaches and for human subject experiments. But this early work is exciting and provides long-term hope for more effective cancer treatments."

Biris, 34, said the UALR Nanotechnology Center's aim is to accelerate the development of commercial applications of nanotechnology and its potential to revolutionize medical advancements and the next generation of manufacturing of other products.

"The close location of UALR with its cutting-edge analytical chemistry and nanotechnological tools, along with UAMS and its established biological and medical infrastructures, provides unique opportunities for comprehensive pre-clinical evaluation of nanotechnological products," Zharov said. "That allows for us to accelerate Nanotechnology advances from bench to bedside, providing breakthroughs in early diagnosis, prevention and effective treatment of cancers, stroke, heart attack, infections, and neurological disorders which remain the leading cause of death in the U.S."

About the scientistsZharov obtained his Ph.D and DSc degrees at Moscow State Technical University and completed a postdoctoral fellowship at Lawrence National Laboratory of the University of California. He served as professor and chairman of the Biomedical Engineering Department at Moscow University. Since 2000, he is a professor and director of the Phillips Classic Laser and Nanomedicine Laboratories at the UAMS Winthrop P. Rockefeller Cancer Institute. Zharov has authored and co-authored five books, 40 patents, and published close to 200 papers. He is the principle investigator in 12 grants from the NIH, NSF, and DoD. He has unique interdisciplinary skills in physics, biology and medicine.

Zharov's research interests include the development and medical application of advanced laser, nanotechnology and imaging and he was the first recipient of the United States Maiman Award, named after the inventor of the first laser. His laboratories have pioneered laser-ultrasound microsurgery, phototherapy of post-mastectomy lymphedema, photoacoustic tweezers, multiplex imaging of cancer cells, laser-gene therapy, laser-based chemosensitivity and radiosensitivity tests, in vivo noninvasive photoacoustic cytometry and blood and lymph cancer tests. In particular, Zharov invented one of the first applications of nanotechnology for treating cancer and infections using laser-activated gold nanoparticles (U.S. Patent, 2000).

Recently, he was awarded by the $1.5 million five-year grant from the National Cancer Institute supporting one of the first clinical application of nanomedicine technology for early cancer diagnosis.

Biris earned his Ph.D. at UALR and joined the faculty in 2006. He and his team have filed 11 patent applications in nanotechnology, bio-nanotechnology, space exploration, and materials science areas. He is fully involved in studying the interaction of nanomaterials with biological systems and using use such novel nanostructures for targeting and killing cancer cells. He has more than 160 papers published in peer reviewed journals or presented at international conferences.

He was part of the team that designed and developed a newly patented electrodynamic screen for space exploration in collaboration with NASA. Patent applications are pending on his new method and technology for producing large quantities of carbon nanotubes with high purity. He led the design and development of carbon nanostructures-based filters to efficiently remove bio-chemical contaminants from air and water.

Biris also developed a unique tissue regeneration system that has been used successfully in 33 clinical studies to grow bone tissue. The work has been licensed to a spin-off company, Orlumet LLC, in which Biris serves as Chief Technical Officer.The co-founder is Peder Jensen.

Biris is honorary president and co-founder of the Romanian Nanomedicine Institute in his native country. In addition to his groundbreaking research and work with graduate and undergraguate students, Biris works one-on-one with gifted middle- and high school students in Arkansas.

He said the key to the Nanotechnology Center at UALR is its aggressive outreach program to train and educate young people and other world-class scientists who will serve and attract business and industry to Arkansas from the region and the nation.

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Journal of Biomedical Optics