Exposing Cancer's Lethal Couriers

Photo: Cancer cells in blood

A team of scientists, engineers and students across five disciplines built nanochains that home in on metastases before they have grown into new tissues, and, through magnetic resonance imaging, detect their locations.

Images of the precise location and extent of metastases could be used to guide surgery or ablation, or the same technology used to find the cancer could be used to deliver cancer-killing drugs directly to the cells before a tumor forms, the researchers suggest.

"Micrometastases cannot be seen with the naked eye, but you have to catch them at this stage – see the exact spots they're located and see them all," said senior author Efstathios Karathanasis. "Even if you miss only one, you prolong survival, but one metastasis can still kill."

Tumor detection technologies fail to uncover cancer cells that have taken hold in new locations because young metastases do not behave the same as established tumors. After a breast cancer cell enters the bloodstream, it most often stops in the liver, spleen or lungs and begins overexpressing surface molecules called integrins. Integrins act as a glue between the cancer cell and the lining of a blood vessel that feeds the organ.

"We target integrins," Karathanasis said. "Normal blood vessel walls do not present integrins towards the blood site unless cancer cells attach there." To home in on the cancer marker, the researchers first needed to build a nano device that would drift out of the central flow of the blood stream and to the blood vessel walls. The most common shape of nanoparticles is a sphere, but a sphere tends to go with the flow.

Karathanasis' team tailored nanoparticles to connect one to another much like a stack of Legos. Due to its size and shape, the oblong chain tumbles out of the main current and skirts along vessel walls. The exterior of the chain has multiple sites designed to bind with integrins. Once one site latches on, others grab hold. Compared to nanospheres, the chains' attachment rate in flow tests was nearly 10-fold higher. To enable a doctor to see where a relative few cancer cells sit in a sea of healthy cells, the scientists incorporated fluorescent markers and, to make the nanochains more visible in magnetic resonance imaging, four links made of iron oxide.

Next, the team tested the chains in a mouse model of an aggressive form of breast cancer that metastasizes to sites and organs much the same way it does in humans. From established research, they knew metastases would be present five weeks into the modeling. They injected nanochains into the bloodstream and, within an hour, two imaging techniques - fluorescence molecular tomography and MRI's - showed where traveling cancer cells had established footholds, primarily in the liver, lungs and spleen.

COMPAMED.de; Source: Case Western Reserve University