A Targeted Cancer Treatment using Nanomaterials

AUGUST 27, 2009

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Optical fluorescent imaging of the TiO2-mAb binding to the single brain cancer cells. The bare titianium dioxide nanoparticle bonds with an antibody and attaches itself to brain cancer cells. When exposed to concentrated white light, the titanium dioxide creates free radicals of oxygen that cause the cancer cells to die. Image courtesy of Argonne National Laboratory.

Thousands of people die from malignant brain tumors every year, and the tumors are resistant to conventional therapies. Now, scientists from the Center for Nanoscale Materials (CNM), Advanced Photon Source (APS), and Chemical Sciences and Engineering Division at the U.S. Department of Energy's Argonne National Laboratory; and the University of Chicago's Brain Tumor Center have developed a way to target brain cancer cells using inorganic titanium dioxide nanoparticles bonded to soft biological material.

This nanobio technology may eventually provide an alternative form of therapy that targets only cancer cells and does not affect normal living tissue.

"It is a real example of how nano and biological interfacing can be used for biomedical application," said scientist Elena Rozhkova of the CNM. "We chose brain cancer because of its difficulty in treatment and its unique receptors."

This new therapy relies on a two-pronged approach. Titanium dioxide is a versatile photoreactive nanomaterial that can be bonded with biomolecules. When linked to an antibody, nanoparticles recognize and bind specifically to cancer cells. Focused visible light is shined onto the affected region, and the localized titanium dioxide reacts to the light by creating free oxygen radicals that interact with the mitochondria (spherical or rod-shaped structures found within the cytoplasm of eukaryotic cells) in the cancer cells. Mitochondria act as cellular energy plants, and when free radicals interfere with their biochemical pathways, mitochondria receive a signal to start cell death.

"The significance of this work lies in our ability to effectively target nanoparticles to specific cell surface receptors expressed on brain cancer cells," said Dr. Maciej S. Lesniak, Director of Neurosurgical Oncology at the University of Chicago Brain Tumor Center. "In so doing, we have overcome a major limitation involving the application of nanoparticles in medicine; namely, the potential of these agents to distribute throughout the body. We are now in a position to develop this exciting technology in preclinical models of brain tumors, with the hope of one day employing this new technology in patients."

X-ray fluorescence microscopy done at the X-ray Operations and Research 2-ID x-ray beamline of APS showed that the tumors' invadopodia, actin-rich micron scale protrusions that allow the cancer to invade surrounding healthy cells, can also be attacked by the titanium dioxide.

So far, tests have been done only on cells in a laboratory setting, but animal testing is planned for the next phase. Results show an almost 100% cancer cell toxicity rate after 6 hours of illumination, and 80% after 48 hours.

Also, since the antibody targets only the cancer cells, surrounding healthy cells are not affected—unlike other cancer treatments such as chemotherapy and radiotherapy.

Rozhkova said that a proof of concept is demonstrated; other cancers could be treated as well, using different targeting molecules, but research is in the early stages.

— Yvonne Carts-Powell

Contact: rozhkova@anl.gov

See: Elena A. Rozhkova, Ilya Ulasov, Barry Lai, Nada M. Dimitrijevic, Maciej S. Lesniak and Tijana Rajh, "A High-Performance Nanobio Photocatalyst for Targeted Brain Cancer Therapy," Nano Letters, Article ASAP, DOI: 10.1021/nl901610f, Publication Date (Web): July 29, 2009;

Funding for this research was through the Department of Energy's Office of Basic Energy Sciences, National Cancer Institute, National Institute of Neurological Disorders and Stroke, Alliance for Cancer Gene Therapy, American Cancer Society and Brain Research Foundation.

Use of the Advanced Photon Source at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences (DOE-BES), under Contract No. DE-AC02-06CH11357.

The Center for Nanoscale Materials at Argonne is one of the five DOE Nanoscale Science Research Centers (NSRCs), premier national user facilities for interdisciplinary research at the nanoscale.  Together the NSRCs comprise a suite of complementary facilities that provide researchers with state-of-the-art capabilities to fabricate, process, characterize and model nanoscale materials, and constitute the largest infrastructure investment of the National Nanotechnology Initiative.  The NSRCs are located at DOE’s Argonne, Brookhaven, Lawrence Berkeley, Oak Ridge and Sandia and Los Alamos National Laboratories.  For more information about the DOE NSRCs, please visit http://nano.energy.gov.

Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America 's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.