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 nanoparticles bonded to soft biological material.
Argonne scientist Elena Rozhkova examines brain cancer cells under a microscope. Rozhkova, along with researchers from the University of Chicago, have developed a way to attach a antibody to nanomaterial titanium dioxide and kill brain cancer cells.
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 application," said scientist Elena Rozhkova with Argonne's
Center for Nanoscale Materials. "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 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 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 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 be also 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 percent cancer
cell toxicity rate after six hours of illumination, and 80 percent after 48
Also, since the antibody only targets 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, and
other cancers can be treated as well using different targeting molecules, but
research is in the early stages.
This work is published in a Nano Letters and is available online at http://pubs.acs.org/doi/full/10.1021/nl901610f.
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.