October 24, 2005

Nanotech Cancer Killers

Multipurpose nanostructures help find, detect, and destroy malignant cells.

By Kevin Bullis

For years now, scientists have been trying to make cancer treatments more effective and reduce their side effects, by packaging drug molecules inside other structures and delivering them only to cancer cells. It's a much-needed effort, since current-day chemotherapy can nearly kill cancer patients, and even the strongest tolerable doses do not destroy some tumors.

But, so far, experimental treatments have helped only with the largest tumors, because the packages are too large to exit the bloodstream easily and infiltrate cells.

Now a researcher and physician at the University of Michigan has shown that manmade molecules called dendrimers can slip out of blood vessels and precisely deliver a drug to tumor cells, at least in mice. The dendrimers can also advertise their locations, allowing researchers to track their progress. The researcher, James Baker, plans to begin human trials in July.

Published last June in Cancer Research, Baker's research helped his laboratory win $2.5 million in a new round of National Cancer Institute (NCI) funding announced last week. His hope is that the funding will push their research to the next level, and eventually give doctors the ability to monitor how individual cells in patients respond to drugs, then tune the treatments accordingly.

Baker's funding is part of a five-year, $144 million NCI project designed to foster the use of nanotechnology to fight cancer. According to the president and chief technical officer of Dendritic NanoTechnologies, Donald Tomalia, who was one of the first to build dendrimers and is still exploring their uses for cancer detection and treatment, out of thousands of experiments published about dendrimers, Baker's recent work has provided "one of the most exciting results." 

Resembling tumbleweeds, dendrimers are clusters of small molecules all linked to a central core. They have multiple attachment sites for other molecules. Baker linked multiple types of molecules to these attachment sites -- over one hundred of the sites -- including one that binds selectively to cancer cells, another that fluoresces (revealing the device's location), and another commonly used as a chemotherapy agent.

In Baker's experiments, the mice receiving traditional chemotherapy all died, from doses that turned out to be either too low or too high. When he used dendrimers, however, to deliver small doses of the drug directly to the cancer cells, some of the mice survived (the number varied according to the experiment). "A tumor that was not treatable with the free drug [was] treatable with the same drug targeted," says Baker.

Because his dendrimers were also fluorescently labeled, Baker was able to see that the drug was indeed being delivered to the cancer cells.

So far, the technique has been shown to work only on head and neck squamous cancer in mice; but similar cancers, such as bladder and ovarian cancer, might also respond.  

Baker's nanotechnology approach overcomes one of the key obstacles to cancer treatment: getting drug molecules inside cancer cells. Because his dendrimers are small -- about the size of a hemoglobin molecule (around 5 nanometers) -- they can readily exit the bloodstream to get to tumors.