Web Date: December 16, 2011
Tumor Tracking Made Easier
To make brain surgery easier and more effective, researchers have designed a nanometer-sized probe that can easily slip into the brain and selectively highlight tumor cells (ACS Nano, DOI: 10.1021/nn203749v).
Before surgeons excise tumors from patients’ brains, they rely on imaging techniques, such as magnetic resonance imaging (MRI), to trace the boundary between cancerous and healthy brain tissue. But distinguishing between the two tissues in the brain is tricky because the small molecule probes that mark tumors have trouble crossing the blood-brain barrier, a physical separation that protects the brain by only allowing specific molecules through. Cong Li of Fudan University in Shanghai, China, and his colleagues wanted to design a tumor nanoprobe that could sneak past this barrier more readily.
The team’s nanoprobes consist of highly-branched polymers called dendrimers labeled with three different types of molecules. The first molecule, a cyclic peptide called RGDyK, would target the probe to the blood vessels surrounding the tumor by binding to receptors on the blood vessels. Once a large number of the nanoprobes have gathered in the blood vessels at the tumor’s edge, another peptide on the probe called Angiopep-2 would bind to receptors that control what gets through the blood-brain barrier. These receptors then would pull the probes past the barrier into the tumor. The final molecules attached to the probe are a set of imaging labels: a fluorescent dye, an infrared dye, and a magnetic resonance imaging agent. With all of these molecules attached to the dendrimer branches, each nanoprobe measured between 11 and 16 nm in diameter.
The researchers tested their probes by injecting them into the bloodstreams of mice that had had human brain tumors grafted into their brains. Within minutes, the researchers could use either MRI or fluorescence microscopy to map the tumors. In both cases, the intensity of signals from the cancerous tissue was significantly greater than that from normal tissue, suggesting that the probes successfully targeted tumors. The tumor images from MRI data also matched those produced when the scientists visually inspected the mouse brains.
“This is a really valuable piece of work,” says chemist Nicholas Long from Imperial College London, who works on medical imaging probes. The nanoprobes are easy to make and handle, he says, “but most importantly, they can cross the blood-brain barrier and stay there.” Long says that the dyes on the probes someday could allow surgeons to check their progress during a tumor operation.
Li says that it will be a while before the probes make it into operating rooms, in part because, his team needs to improve their synthesis to ensure that the probes are identical and contain each of the three molecule types.
- Chemical & Engineering News
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