Telegraph (KC) 07-Jul-08

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Nanoparticle smart bombs used to target cancer cells

By Roger Highfield, Science Editor

Smart bombs consisting of microscopic particles can curb the deadly spread of cancer, a team reports today.

The smart bombs are nanoparticles, that is particles at the length scale of a billionth of a metre or so, and can be used to target malignant cancer cells as they move through the body, a process called metastasis that seeds new tumours throughout the body.

A new treatment strategy using polymer particles 100 billionths of a metre across to bombard tumour cells with anti-cancer drugs leads to good results, using significantly lower doses of toxic chemotherapy, with less "collateral damage" to surrounding tissue, researchers report today.

The team, led by Prof David Cheresh of the University of California, San Diego, showed this way to ensure toxic chemotherapy is delivered precisely where it is needed had "a profound impact on metastasis in pancreatic and kidney cancer in mice."

An American company, Kereos in St Louis has developed commercial forms of similar nanoparticles and is now preparing for clinical trials on patients.

In a study in the Proceedings of the National Academy of Sciences, Prof Cheresh and members of his team report that the nanoparticle-carrying a payload of chemotherapy homes in on a protein called integrin ανβ3 that is found on the surface of certain tumour blood vessels, where it boosts the development of new blood vessels to nurture the tumour and to speed malignant growth.

When chemotherapy is injected into the blood stream, the body is flooded with cancer-killing toxins. When the toxins were linked to the nanoparticle, the combination only had a modest impact on primary tumours but it did stop pancreatic and kidney cancers from spreading throughout the bodies of mice. They showed that a greatly reduced dosage of chemotherapy can achieve the desired effect, because the drug selectively targets the specific blood vessels that feed the secondary cancer cells without destroying surrounding tissue.

"We were able to establish the desired anti-cancer effect while delivering the drug at levels 15 times below what had been used previously," said Prof Cheresh.

"Even more interesting, was that the metastatic lesions were particularly susceptible to this therapy.” The team used doxorubicin, which is known to be an effective anti-cancer drug, but has been difficult to give patients an adequate dose without negative side effects. "This new strategy represents the first time we’ve seen such an impact on metastatic growth, and it was accomplished without the collateral damage of weight loss or other outward signs of toxicity in the patient," said Prof Cheresh.

Cancer metastasis is traditionally much more difficult to treat than the primary tumour, and is what usually leads to the patient’s death.

But Prof Cheresh believes that, because metastasis is more reliant on new blood vessel growth than established tumours are, targeting the anti-cancer drug to the sites of new blood vessel growth has a preferential effect on cancer cell that have spread.

"Traditional cancer therapies are often limited, or non-effective over time because the toxic side effects limit the dose we can safely deliver to the patient," said Prof Cheresh.

"This new drug delivery system offers an important advance in treating metastatic disease."

Additional contributors to the study were Eric Murphy, Bharat Majeti, Leo Barnes, Milan Makale, Sara Weis and Wolfgang Wrasidlo, all of the UCSD Cancer Centre. The study was supported by the National Institutes of Health and the National Cancer Institute Nanotechnology Alliance.

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