Jul 9 2008
A team of researchers in the U.S. have developed a nanoparticle with the ability to precisely deliver cancer-fighting drugs.
The new treatment uses molecular "smart bombs" to target a tumour's blood vessels and this stops tumours from metastasizing, or spreading through the body.
The "smart bombs" are loaded with anti-cancer drugs and use significantly lower doses of toxic chemotherapy, which results in less collateral damage to the surrounding tissue.
The team from the University of California, San Diego, say their "nanoparticle" drug delivery system has identified a way to target chemotherapy and say in trials with mice the smart bombs had a profound impact on metastasis in pancreatic and kidney cancers.
Dr. David Cheresh, who led the research, says the nanoparticle carrying a payload of chemotherapy targets a protein marker called integrin áíâ3, which is found on the surface of certain tumour blood vessels where it is associated with development of new blood vessels and malignant tumour growth.
Cheresh and his team found that while the nanoparticle/drug combo had little impact on primary tumours, it stopped pancreatic and kidney cancers from metastasizing throughout the bodies of mice.
They also showed that this effect was achieved with a far smaller dose of chemotherapy because the drug selectively targets the specific blood vessels that feed the cancerous lesion and kills the lesion without destroying surrounding tissue.
An unwanted side-effect of chemotherapy is the destruction of healthy tissue when it is administered systemically, which floods the body with cancer-killing toxins.
Dr. Cheresh says they were able to establish the desired anti-cancer effect by delivering the drug at levels 15 times below what is needed when the drug is used systemically and says it is interesting that the metastatic lesions were more sensitive to this therapy than the primary tumour.
The research was a collaborative endeavour linking researchers from UC San Diego's Health Sciences and the Jacobs School of Engineering, where engineers and oncologists worked together to design the nanoparticle.
The nanoparticle - a microscopic-sized particle of 100 nanometers - is made of various lipid-based polymers which delivers the cancer cell-killing drug doxorubicin to the network of blood vessels supporting the tumour that express the áíâ3 protein.
Dr. Cheresh says doxorubicin is known to be an effective anti-cancer drug, but it has been difficult to give patients an adequate dose without negative side effects and the new strategy represents the first time such an impact on metastatic growth has been seen without the collateral damage of weight loss or other outward signs of toxicity in the patient.
Experts say cancer metastasis is much more difficult to treat than the primary tumour, and is what usually leads to the patient's death.
Because metastasis is more reliant on new blood vessel growth than established tumours are, Dr. Cheresh suspected that targeting the anti-cancer drug to the sites of new blood vessel growth could be more effective.
Dr. Cheresh says traditional cancer therapies are often limited, or non-effective over time because the toxic side effects limit the dose which can be safely delivered to the patient and this new drug delivery system offers an important advance in treating metastatic disease.
The study was supported by the National Institutes of Health and the National Cancer Institute Nanotechnology Alliance and is published in the Proceedings of the National Academy of Sciences (PNAS).
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