Titanium Dioxide Nanoparticles Catalyze Brain Tumor Death

Sep 24, 2009

(PhysOrg.com) -- Scientists from the U.S. Department of Energy’s (DOE) Argonne National Laboratory and the University of Chicago Medical Center’s Brain Tumor Center have developed a way to target brain cancer cells using inorganic titanium dioxide nanoparticles bonded to antibodies. Thousands of people die from malignant brain tumors every year, and the tumors are often resistant to conventional therapies. These composite nanoparticles eventually may 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 Argonne’s Elena Rozhkova, Ph.D., who led the study. “We chose brain because of its difficulty in treatment and its unique receptors.” The results of this study were published in the journal Nano Letters.

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 cells,” said Maciej S. Lesniak, M.D., of the University of Chicago Medical Center’s 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 performed 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, also can be attacked by the nanoparticles. So far, tests have been done only on cells in a laboratory setting, but animal testing is planned for the next phase. Following a 5-minute exposure to focused lights, there was an almost 100% cancer cell toxicity rate 6 hours after exposure and 80% toxicity 48 hours after exposure. Also, since the antibody targets only the —unlike other cancer treatments such as chemotherapy and radiotherapy—surrounding healthy cells are not affected.

This work, which is detailed in the paper “A high-performance nanobiophotocatalyst for targeted brain cancer therapy,” was supported by the National Cancer Institute. An abstract is available at the journal’s Web site.

Provided by National Cancer Institute (news : web)

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User comments : 6

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Adriab
not rated yet Sep 24, 2009
Wow, today is seeing some big news so far. This article, the one about an advance in AIDS vaccination, water in moon rocks. Good stuff all of it.

The one thing that bothers me is that it isn't bigger news. Or at least more talked-up in the media.

Directly relating to this article: where does the TiO2 go after it kills the tumour? Does the immune system dispose of it, is it flushed out in the blood to the kidneys? Or does it just build up in the brain?
Birger
not rated yet Sep 24, 2009
"Mitochondria act as cellular energy plants, and when free radicals interfere with their biochemical pathways, mitochondria receive a signal to start cell death"
Just a question, are not mitochondria de-activated in most cancers?
El_Nose
not rated yet Sep 24, 2009
great start -- just how to turn a light on in the cranium.
E_L_Earnhardt
not rated yet Sep 25, 2009
Mitochondria are NOT deactivated in a cancer condition. Their electrons are just not needed to start mitosis with all the "free electrons" braking
hydrogen bonds to accelerate mitosis. Drain off the excess electrons and mitochondria regains control. "Cooling" is the best drain I know!
MongHTanPhD
not rated yet Sep 25, 2009
RE: In vitro tests may not directly translate into in vivo successes! [post 1]

This is only a preliminary testing of an anticancer effect in test tube:
So far, tests have been done only on cells in a laboratory setting, but animal testing is planned for the next phase.
It still has hurdles, like the blood-brain barrier to cross; lest these tumor specific agents could be applied intra-tumorally. [to be continued in post 2]
MongHTanPhD
not rated yet Sep 26, 2009
RE: In vitro tests may not directly translate into in vivo successes! [post 2]

Their predictions of the in vitro comparing to in vivo outcomes:
Following a 5-minute exposure to focused lights, there was an almost 100% cancer cell toxicity rate 6 hours after exposure and 80% toxicity 48 hours after exposure.
[to be continued in post 3]

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