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Watching Cancer Cells Die

Is a cancer treatment actually helping? Nanoparticles that detect cell death may supply a quick answer.

Cancer patients often suffer for months before finding out whether or not a treatment is helping. If oncologists could see what was happening to tumor cells immediately after a treatment – whether they were flourishing or dying – the physician could quickly switch patients’ drugs, if needed. Researchers have now developed a nano sensor that could be used with MRI imaging to check whether tumor cells are dying.

The nano sensor, developed by scientists at the Center for Molecular Imaging Research at Harvard University and Massachusetts General Hospital, detects a kind of systematic cell suicide called apoptosis. The nano sensor could directly signal whether a drug is working or not by looking at individual cells. The detector uses an iron-oxide nanoparticle; on its surface are about 15 peptides that attach to a lipid called phosphatidylserine that appears on human cell membranes during apoptosis.

Ching Tung, associate professor of radiology at Harvard Medical School, who developed the nano sensor, says his group should also be able to see the sensors inside the human body using MRI because “the iron-oxide particle is a very good imaging contrast agent for MRI.” After a patient has been on a cancer treatment for a few days, he or she could be given the nano sensor and an MRI scan could show whether tumor cells are dying.

Currently, the only way to know if a cancer drug is working is to wait weeks or months until it causes a significant change in tumor size that can be picked up by conventional imaging. “To see a tumor shrink from one centimeter to half a centimeter, you need to wait a long time,” Tung says. Staying on a treatment regimen that’s not working is dangerous for patients. They suffer both the effects of a tumor that continues to grow and the side effects of the ineffectual drug. Worse, weeks or months of a failing treatment regimen can trigger defense mechanisms by the tumor cell that may render ineffectual a second-line therapy that might have otherwise worked.

The work by Tung and his colleagues is part of a larger effort in the cancer research community to use nanoparticles to detect the presence and measure the activity of tumor cells through imaging technologies. To that end, the National Cancer Institute (NCI) has pledged $26.3 million over the past year to establish eight Centers of Cancer Nanotechnology Excellence, including a center jointly led by Harvard and MIT.

So far, Tung and his coworkers have tested the nano sensor on human leukemia cells in the lab. They attached a fluorescent tag to the peptides so they could tell when the nano sensors had found cells undergoing apoptosis. “Our next step is to use these complexes for in vivo imaging, first in animals, using the MRI approach to see which part of the organ or any tissues is going through apoptosis,” says Tung. Nanoparticles very similar to the iron oxide in their sensors have been approved for use in humans; the peptides, which Tung’s group designed for their experiments, have not.

Indeed, these are early days in the development of Tung’s nano sensor. But Piotr Grodzinski, director of Nanotechnology for Cancer programs at the NCI’s Alliance for Nanotechnology in Cancer, says that if the iron-oxide nanoparticles in the nano sensor do indeed improve the resolution of MRI imaging, the research “is very relevant.”

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