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Nanomedicine Tackles Brain Cancer:
Gold Nanoparticle-Enhanced
Radiation Therapy with AuroVist™

Gold nanoparticles are being used to magnify the effects of radiation therapy in brain cancer, nearly doubling the gains in survival time of test animals.

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Brain cancer has a potent new enemy: gold nanoparticles.

New research from Dr. Hélène Elleaume's lab (Bobyk, 2013) at the INSERM Grenoble Institut des Neurosciences in France, shows that injecting brain tumors with gold greatly increases the effectiveness of subsequent radiation therapy. The key is that gold strongly absorbs X-rays during treatment; it then re-releases the accumulated energy locally, delivering a magnified dose of radiation to the tumor. This enhancement of radiotherapy works powerfully against cancer: the gold nanoparticle treatment nearly doubled the increase in lifespan afforded by radiation alone.

Gold nanoparticle therapy for a deadly and difficult to treat cancer

Brain cancer is among the most deadly and difficult to treat of cancers. Patients with glioblastoma multiform (GBM), one of the most aggressive types, survive on average only 12 – 15 months after diagnosis, and most such tumors recur, despite postsurgical radiation treatment and chemotherapy.

Finding an effective treatment has so far been elusive, with researchers forced to find very precise interventions with brain tissue, where every neuron is precious. The idea of using gold to concentrate radiation meets this challenge: each gold nanoparticle will focus radiation damage within the radius of a few cells, keeping collateral damage to a minimum.

Another difficulty with brain tumors is the blood-brain barrier, which blocks most therapeutic agents from entering the brain from the bloodstream. Researchers at Nanoprobes proved that their 15 nm gold nanoparticles will successfully cross the compromised blood-brain barrier into brain tumors after an IV injection (Hainfeld, 2013), but Bobyk et al. chose to directly inject into the tumors themselves. They used a method called convection-enhanced delivery to load rat brain tumors with Hainfeld et al.'s gold nanoparticles, made available for research as AuroVist™ 15 nm (Nanoprobes).

Tuning to Gold: Using low-energy X-rays
at the European Synchrotron Radiation Facility

The next step was applying radiation to the gold-laden brain cancers. The machines used in most clinics produce X-rays with too much energy, so the team turned to the European Synchrotron Radiation Facility in Grenoble, France. There, a lower energy beam of 88 keV could be used, delivering just the right amount of radiation for the gold to absorb and then release in a tiny burst, damaging only adjacent cells. To test their approach, the animals were delivered a total dose equivalent to that used in clinical radiotherapy.

Gold nanoparticles enhance radiation, without toxicity

The results were very encouraging. Without treatment, the test animals with brain tumors survived an average of only 24 days; with radiation alone, for 33 days. When the gold nanoparticles were paired with radiation, however, the mean survival time surged to 42 days—effectively doubling the increase in lifespan afforded by radiotherapy. In addition to therapeutic efficacy, the researchers found that the AuroVist™ 15 nm gold nanoparticles were well tolerated, with no significant toxicity issues apart from a small weight loss even at the highest dose used.

Gold-enhanced radiation therapy, or GERT, is a promising new line of attack on brain cancer, one of the most difficult cancers to treat. Previous studies have found similar gains in efficacy: Dr. James F. Hainfeld of Nanoprobes, who created AuroVist™, was the principal investigator in another successful GERT-brain cancer study earlier this year.

"It's great to see confirmation of this approach," said Dr. Hainfeld. "Magnifying the effects of radiation can make a huge difference in the success of treatment. There's real hope here, and we congratulate Bobyk and Elleaume's success in obtaining these promising results."



Bobyk L.; Edouard M.; Deman P.; Vautrin M.; Pernet-Gallay K.; Delaroche J.; Adam J. F.; Estève F.; Ravanat J. L., and Elleaume, H.: Photoactivation of gold nanoparticles for glioma treatment. Nanomedicine, 9, 1089-1097 (2013).

Hainfeld JF, Smilowitz HM, O'Connor MJ, Dilmanian FA, Slatkin DN. Gold nanoparticle imaging and radiotherapy of brain tumors in mice. Nanomedicine (Lond). 2013 Oct; 8(10):1601-9.



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