Scientists from the U.S. Department of Energy’s (DOE) 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 (TiO₂) nanoparticles bonded to soft biological material. Thousands of people die from malignant brain tumors every year, and the tumors are resistant to conventional therapies. This nano-bio 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 applications,” said Elena Rozhkova, a scientist with Argonne’s Center for Nanoscale Materials. “We chose brain cancer because of its difficulty in treatment and its unique receptors.”

Targeting Cancer

Enlarge this picture Figure 1. When bonded to an antibody, the nanomaterial attaches and kills brain cancer cells.

The new therapy relies on a two-pronged approach. TiO₂ is a versatile photoreactive nanomaterial that can be bonded with biomolecules. When linked to an antibody, the nanoparticles recognize and bind specifically to cancer cells (see Figure 1). Focused visible light is shined onto the affected region, and the localized TiO₂ reacts to the light by creating free oxygen radicals that interact with the mitochondria 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 Maciej S. Lesniak, Ph.D., 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.”

Enlarge this picture Figure 2. X-ray fluorescence imaging of the TiO2-bonded antibody binding to the single brain cancer cells.

X-ray fluorescence microscopy done at Argonne’s Advanced Photon Source also 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 TiO₂ (see Figure 2). In addition, since the antibody only targets the cancer cells, surrounding healthy cells are not affected, unlike other cancer treatments such as chemotherapy and radiotherapy.

Future Potential

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 six hours of illumination, and 80% after 48 hours. Though research is in the early stages, Rozhkova said that a proof of concept is demonstrated and it’s possible that other cancers could be treated as well using different targeting molecules.

The work was published in Nano Letters. Funding for the research came through the DOE’s Office of Basic Energy Sciences, the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, the Alliance for Cancer Gene Therapy, the American Cancer Society and the Brain Research Foundation.

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