Device can absorb drugs after targeting tumors

That's after a separate tube delivers a more concentrated dose to tumors—and before the drugs can widely circulate in the bloodstream.

Researchers say the drug-capture system could also potentially be applied to antibiotic treatments in combating dangerous bacterial infections while limiting their side effects.

X. Chelsea Chen, a postdoctoral researcher working in the Soft Matter Electron Microscopy program in Berkeley Lab's Materials Sciences Division, had been investigating polymer membranes—which help current to flow in a fuel cell that converts hydrogen and oxygen into electricity—when she learned about the concept for this new type of medical device.

She saw that the proposed drug-capture device could benefit from the same property in the fuel cell material, which allows it to attract and capture certain molecules by their electric charge while allowing other types of molecules to flow through.

The polymer material includes polyethylene, which is strong and flexible and is used for garbage bags, and another polymer containing sulfonic acid, which has a negative electric charge.

Certain types of chemotherapy drugs, such as doxorubicin, which is used to treat liver cancer, have a positive charge, so the polymer material attracts and binds the drug molecules. "In our lab experiments, the current design can absorb 90% of the drug in 25-30 minutes," Chen said.

That is important, since an increasingly popular liver-cancer treatment, known as TACE, can allow up to half of the chemotherapy dose to reach the rest of the body even though it is intended to reduce its circulation.

"Doxorubicin has been around for decades. It is very well understood, and it is also very toxic," said Steven Hetts, an associate professor of radiology at UC San Francisco and an interventional neuroradiologist at the UCSF Medical Center who conceived of the new treatment system, called ChemoFilter. "If you get exposed to too much, when it goes through the heart you can go into heart failure." So doctors are very careful with the dose.

Hetts specialises in treating eye tumors by navigating a tube, called a catheter, from the femoral artery in the thigh to the opthalmic artery that supplies blood to the affected eye, and pumping chemotherapy medication through the catheter to the tumor.

While the eye cancers he treats are rare—there are several hundred children per year in the U.S. who are affected by this kind of tumor—he saw a parallel need to improve the treatment options for liver cancer, which is far more pervasive: It is the third-leading cause of cancer deaths globally, with an estimated half a million new cases each year.

In 2013 his staff reached out to Nitash Balsara, a senior scientist at Berkeley Lab and a chemical engineering professor at UC Berkeley and lead-PI of the Soft Matter Electron Microscopy program in Berkeley Lab's Materials Sciences Division, to pursue the idea, and Chen began to work on materials based on Hetts' concept. The research team received a patent for a ChemoFilter system in April.

The patented device features a nickel-titanium metal frame in a collapsible flower-petal array, attached to a thin polymer membrane that can be expanded out from a catheter to absorb a drug. In a preclinical study, a ChemoFilter device was inserted into a pig and was found to reduce the peak concentration of the chemotherapy drug doxorubicin by about 85%. The device will hopefully find use in human cancer treatment within a couple of years, Hetts said.

Chen and other researchers are also working on next-generation ChemoFilter devices that use a different mix of materials and different methods to remove drugs from the body, though those will likely take longer to receive federal approval for use.

The membranes could also be designed to capture antibiotics to treat potentially deadly infections from anthrax and other bacteria, and there are many applications in veterinary medicine, too, he said.

Chen uses facilities at Berkeley Lab's Molecular Foundry to develop specialised polymers for ChemoFilter devices. She also uses the Foundry's National Center for Electron Microscopy and conducts X-ray experiments at the lab's Advanced Light Source and SLAC National Accelerator Laboratory's Stanford Synchrotron Radiation Lightsource to study the nanostructure of the polymer materials she develops, and to better understand the drug-capture mechanism at microscopic scales and inform new designs.

"We are actively searching for new materials and mechanisms" for the polymer membranes, she added. Researchers are exploring the use of 3D-printed materials, for example, that can be coated with charged particles to attract and bind drug molecules.