Nanoparticles fight cancer cells with lethally high ‘fever’

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BERLIN, Sept. 11, 2003 – Scientists in Germany have developed a new cancer-fighting technique using nanoparticles injected into tumors to give malignant cells a high “fever” they can’t survive.

It might be called a Trojan horse strategy. Scientists at Berlin’s Charité Hospital are using the particles, made of iron oxide, to battle a particularly aggressive form of brain cancer called glioblastoma. The strategy also could be used to treat other forms of cancer. Some scientists, however, are advising caution.
The new procedure, which is just entering the clinical trial phase in Berlin, involves coating the tiny iron oxide particles with an organic substance, in this case, glucose. They then are injected into a malignant tumor. The tumor, which has a fast metabolism and correspondingly high energy needs, greedily sucks up the little particles masquerading as sugar pellets of a sort. Healthy cells, on the other hand, show little interest. The voraciousness of the cancerous cells proves to be the tumor’s downfall. 
After the nanoparticles have ensconced themselves in the malignant tissue, scientists use a magnetic field to heat them to temperatures approaching 45 degrees Celsius (113 degrees Fahrenheit). It has the effect of giving the cells a fever that causes significant damage. Cancer cells are ferocious, but scientists have long known that heat is their Achilles’ heel.
The heat destroys many of the cancer cells in and around the tumor or weakens them to a point that they are more effectively treated with radiation or chemotherapy.
The treatment, known as magnetic fluid hyperthermia, was first successfully used in extending the lives of laboratory rats implanted with malignant brain tumors. The rats receiving the nanotherapy lived four times as long as rats receiving no treatment.

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In a first test on humans, the nanoparticle therapy used in combination with traditional radiation therapy succeeded in destroying a tumor in the shoulder of a 26-year-old man.

“According to tests, he’s tumor-free,” said Dr. Andreas Jordon, a biologist working on the project. “But it doesn’t yet lead us to any far-reaching conclusions.” 
The hospital is planning to test the technique on 15 patients who are suffering from glioblastoma multiforme, the most common primary brain tumor and the most aggressive form of brain cancer. The life expectancy prognosis in human patients is on average six months to one year. The trials are expected to begin in one or two months.
“We expect the new method to extend the life expectancy of glioblastoma patients,” said Klaus Maier-Hauff, director of the project and head of neurosurgery at the teaching wing of the Charité hospital.
The treatment is particularly attractive to doctors working with tumors in the brain since the nanoparticles are placed in the malignant tissue by means of an extremely precise electronic navigation system. That means they can reach tumors that lie outside the reach of conventional surgical treatment, such as those situated deep in the brain or in regions that are responsible for essential tasks like speech or motor functions.
But the heat therapy theoretically is not limited to types of brain cancer. Scientists who work with breast cancer are preparing to adopt the therapy for their own patients.
“I won’t have to remove the breast if I can also work in a non-invasive way,” said Ingrid Hilger of the Institute for Diagnostic and Intervention Radiology at the University of Jena.
She hopes that the treatment will be especially effective with breast cancer patients, since breast tumors do not lie in the immediate vicinity of essential organs. Therefore it would be possible to use higher temperatures when heating the malignant tissue.
“Ideally that means we could dispense with parallel treatments with radiation and chemotherapy,” she said.
Some scientists however are warning against too much euphoria, saying the iron oxide nanoparticles used in the treatment could do damage to other tissues of the body if they reach the bloodstream.

“The tumor researchers are using nanoparticles like they are harmless substances,” said Paul Born of the Düsseldorf-based Environmental Health Research Institute. “They are overlooking the particles’ potential toxic properties.”

He points to the work of researchers at the Institute for Toxicology and Genetics in Karlsruhe, Germany, whose experiments with human lung tissues came to the conclusion that the smaller the particle, the more dangerous it could be to the human body.

But scientists working on the new therapy project say the dangers of poisoning are low.

“Nanoparticles are already used in magnetic resonance therapy for the diagnosis of liver tumors,” said Hilger. “That shows us that there’s no danger to health as long as the amount of metal introduced in the body is kept under a certain level.”


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