Tuesday, October 28, 2008

Killing Cancer Cells Using Cobalt Nanoparticles Coated with Graphitic Shells

A team of scientists at Arkansas Nanotechnology Center at UALR (the University of Arkansas at Little Rock) has developed what promises to be a non-invasive method of eradicating cancer cells while reducing the life-threatening side effects of chemotherapy and radiation.

The new technique, described in the current issue of the journal Nanotechnology, was developed by a team led by Dr. Alexandru Biris, assistant professor of applied science and chief scientist at the Nanotechnology Center. Working in collaboration with the University of Arkansas for Medical Sciences, the team successfully killed more than 98 percent of the cervical cancer cells used in the study.

The technique introduces nano-sized cobalt particles encased in graphitic carbon layers inside the cells and thermally activates them by using radio frequency radiation. By applying low radio frequency radiation – used in some electronic or electromagnetic devices – the magnetic portion in the nanoparticles heats up the cancerous cells, destroying them.

The procedure promises a non-invasive method of eradicating cancer cells while reducing the life-threatening side effects of chemotherapy and radiation.

The technique is described in their new research paper, Cobalt Nanoparticles Coated with Graphitic Shells as Localized Radio Frequency Absorbers for Cancer Therapy.

"We have demonstrated that using a combination of a low frequency, low power radio frequency radiation – which has a high penetration ability in human tissue – with graphitic-magnetic composite nanoparticles could prove an excellent means of raising the temperature at the cellular level above the threshold required for DNA fragmentation or protein denaturation,” Biris said. “The result is death of the cells. This technique is less invasive and possesses higher efficiency for targeting localized cells. It also has the potential to reduce the side effects associated with traditional cancer therapies.”

With approved research protocols, UAMS scientists are expanding on previous work involving use of nanostructural materials for killing tumors with lasers. Using this method, the nanomaterials are introduced through the bloodstream to be activated with radio frequency energy once they are in the tumors.

“We believe this method is extremely promising for killing cancer cells,” said Dr. Vladmir Zharov, professor and director of the Phillips Classic Laser Laboratories in the UAMS Winthrop P. Rockefeller Cancer Institute. “We are working now to move this technology toward clinical trials with the ultimate goal of achieving a safe, effective procedure that leaves a patient cancer free.”

Biris, a native of Romania who earned a Ph.D. in applied science at UALR in 2004, said the delivery of the encased nanoparticle to tumors will also be explored by binding them to cancer-specific antibodies.

By using antibodies or other nanoparticle bioconjugations – the coupling of two substances – the nanoparticles are expected to find the cancer cells even in advanced cases, including places that before now have been considered inoperable. The nanoparticles can also find undiagnosed micrometastasis, or the spread of cancer cells from the primary site with the secondary tumors too small to be detected clinically.

“This research has extended the understanding of the mechanisms that are responsible for effective nanoparticle targeting and eventually the death of cancer cells,” Zharov said.

The team’s work is helping to explain the mechanism that is responsible for the death of the cells by figuring out the localized thermal damages such as protein denaturation and DNA fragmentation associated with the process. The finding can be applied to bacteria, viruses, or other biological systems.

Members of the research team working with Biris are:

* Yang Xu, Meena Mahmood, Zhongrui Li, and Enkeleda Dervishi, Nawab Ail, and Viney Saini, all of all of the Nanotechnology Center and Department of Applied Science at UALR.
* Vladimir P. Zharov’ group: Ekaterina Galanzha and Evgeny Shashkov, the Philips Classic Laser Laboratories at UAMS.
* Steve Trigwell of ASRC Aerospace, NASA’s Electrostatic and Surface Physics Laboratory at Kennedy Space Center in Florida.
* Alexandru R. Biris and Dan Lupu of the National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj Napoca, Romania.
* Dorin Boldor of Louisiana State University’s AgCenter, Biological and Agricultural Engineering Department in Baton Rouge, LA.

To read Biris’ paper, visit http://www.iop.org/EJ/journal/Nano.

Posted October 28th, 2008


Cobalt nanoparticles coated with graphitic shells as localized radio frequency absorbers for cancer therapy

Yang Xu et al 2008 Nanotechnology 19 435102 (9pp) doi: 10.1088/0957-4484/19/43/435102 Help

PDF (1.18 MB) | Supplementary data | References

Yang Xu1, Meena Mahmood1, Zhongrui Li1, Enkeleda Dervishi1, Steve Trigwell2, Vladimir P Zharov3, Nawab Ali1, Viney Saini1, Alexandru R Biris4, Dan Lupu4, Dorin Boldor5 and Alexandru S Biris1
1 Nanotechnology Center and Applied Science Department, University of Arkansas at Little Rock, Little Rock, AR 72204, USA
2 NASA, Electrostatics and Surface Physics Laboratory, ASRC Aerospace, Kennedy Space Center, FL 32899, USA
3 Philips Classic Laser Laboratories, University of Arkansas for Medical Sciences, Little Rock, AR 72204, USA
4 National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj Napoca, RO-3400, Romania
5 Louisiana State University, AgCenter, Baton Rouge, LA, USA
E-mail: yxxu@ualr.edu and asbiris@ualr.edu

Abstract. Graphitic carbon-coated ferromagnetic cobalt nanoparticles (C–Co-NPs) with diameters of around 7 nm and cubic crystalline structures were synthesized by catalytic chemical vapor deposition. X-ray diffraction and x-ray photoelectron spectroscopy analysis indicated that the cobalt nanoparticles inside the carbon shells were preserved in the metallic state. Fluorescence microscopy images and Raman spectroscopy revealed effective penetrations of the C–Co-NPs through the cellular plasma membrane of the cultured HeLa cells, both inside the cytoplasm and in the nucleus. Low radio frequency (RF) radiation of 350 kHz induced localized heat into the metallic nanoparticles, which triggered the killing of the cells, a process that was found to be dependent on the RF application time and nanoparticle concentration. When compared to carbon nanostructures such as single-wall carbon nanotubes, these coated magnetic cobalt nanoparticles demonstrated higher specificity for RF absorption and heating. DNA gel electrophoresis assays of the HeLa cells after the RF treatment showed a strong broadening of the DNA fragmentation spectrum, which further proved the intense localized thermally induced damages such as DNA and nucleus membrane disintegration, under RF exposure in the presence of C–Co-NPs. The data presented in this report indicate a great potential of this new process for in vivo tumor thermal ablation, bacteria killing, and various other biomedical applications.

Print publication: Issue 43 (22 October 2008)
Received 17 July 2008, in final form 25 August 2008
Published 22 September 2008