Scientists have developed a titanium dioxide-based nanomaterial that kills cancer cells and leaves healthy cells unharmed.
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 (TiO
2) 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.”

Figure
1. When bonded to an antibody, the nanomaterial attaches and kills brain cancer
cells.
Targeting Cancer
The new therapy relies on a two-pronged
approach. TiO
2 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 TiO
2
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.”

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 TiO
2 (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.
Visit www.anl.gov or www.uchospitals.com for more
information.Links