A new nanotechnology-based treatment developed by researchers at the University of Texas’s Southwestern Medical Center at Dallas could double the effectiveness of cancer drugs without increasing side effects, while allowing doctors to see immediately whether the treatment is working.
Nanotechnology-based drug treatments are already starting to be approved for use, but so far they are neither very precise nor very potent. Current cancer-fighting nanomedicine, which involve little more than nanoscopic containers packed with chemotherapy drugs, reaches tumors by leaking through holes in tumor blood vessels and gradually releasing a drug. To kill appreciable amounts of the tumor this way, doctors must flood the body with these drug-bearing nanocarriers, says Jinming Gao, associate professor of oncology and pharmacology at the University of Texas Southwestern Medical Center at Dallas. These can get soaked up by the body’s natural filters, such as the liver and spleen, in which they can cause side effects, he says.
What’s more, doctors can’t get a good view of what’s happening once nanocarriers are administered. They don’t know whether the nanocarriers are reaching targets or delivering drugs until they remove tissue from the patient, the tumor starts to shrink, or the first side effects appear. It’s like fighting cancer in a “black box,” Gao says.
Now a growing cadre of researchers are developing next-generation nanomedicine platforms that can both deliver drugs only to cancer cells and allow doctors to monitor the progress of the treatment. The University of Texas system delivers both an anti-cancer drug and a highly effective magnetic resonance imaging (MRI) contrast agent to allow doctors to see that the drug is being delivered to a tumor. The nanocarriers are made of polymers with an inner core that traps doxorubicin, a common chemotherapy drug, and iron-oxide particles that show up clearly with MRI. Polymer strands on the outside of the nanocarrier bear targeting molecules that are recognized only by tumor blood-vessel cells. The nanocarriers latch on to the vessel cells, and the cells engulf the carriers. The polymer releases the drug once inside the cell, where it is most effective.
Tests on cells grown in the lab showed promising results, says Gao. Nanocarriers equipped with the targeting molecule delivered twice the amount of drug and killed twice the number of cells (94 percent) as those without it, he reported online in the journal Nano Letters.”We could detect as few as 50,000 cells,” Gao says. Studies in mice are now in progress.
At this point, the nanocarriers only target tumors’ blood vessels, so they can’t image or attack tumors without vasculature. This includes most tumors smaller than about two cubic millimeters. But Gao says tumors in the dangerous process of spreading, or metastasizing, are large, have well-established vessels, and can be directly attacked.
And unlike other targeted cancer therapies, he adds, the nanocarriers are easy to modify. As researchers discover more targets unique to cancer cells, the nanocarriers can be equipped to find, image, and destroy other types of cells within tumors and also different types of cancer, he says. He is now working on a system that directly targets lung-cancer cells.
The clearer images created by nanoparticles delivered directly into cancer cells could ultimately allow many new possibilities, says Michael Bonder, a postdoctoral researcher at the University of Delaware’s Cancer Translational Research Center. Doctors could detect smaller tumors and possibly watch them metastasize, or spread cell by cell to new parts of the body.
But toxicity remains a risk, even with the targeted nanocarriers, cautions Glen Kwon, associate professor of pharmaceutics at the University of Wisconsin. He says Gao’s team should run tests to ensure that minimal amounts of the drug leak out as the nanocarriers travel through the bloodstream. “This is often a major challenge for nanocarrier systems in drug delivery,” Kwon says.
Patrick Winter, assistant professor of medicine at Washington University in St. Louis, adds that it’s questionable how many nanocarriers will reach their target. “Even the best targeting strategies” only get a small fraction of the nanocarriers into the tumor, and the rest end up in normal tissues, he says. No matter how well the new nanocarriers perform, some will likely end up in “clearance organs like the liver and spleen,” which “could lead to side effects,” he says.
Gao counters that so few nanocarriers will be injected that even if a large fraction missed their target, no side effects would occur.
But the new nanocarriers are promising as “a triple threat to a cancer cell,” says Robert Sikes, director of the Laboratory for Cancer Ontogeny and Therapeutics at the University of Delaware. “They seek out, display the location, and deliver the lethal blow to dividing cancer cells,” he says.
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