New battery starves cancer cells of oxygen in mice

It’s not great when one person sucks all the oxygen out of a room. When a battery does it on a tumor, that could be a good thing.

A tiny, self-charging battery wrapped around a tumor removes oxygen from the environment of cancer cells, boosting the potency of some cancer therapies, a study in mice has found. Mice that had small piles wrapped around their cancerous breast tumors, combined with cancer treatment, showed a 90% decrease in tumor volume in two weeks, researchers report March 31 to Scientists progress.

Solid tumors, such as those that can develop into breast canceroften grow rapidly – so rapidly that the tumor grows faster than its blood supply can support (SN: 5/10/17). This means that the center of many tumors can be hypoxic, with much lower oxygen levels than surrounding tissue.

“Hypoxia is a double-edged sword,” says materials scientist Yongyao Xia, who specializes in battery materials at Fudan University in Shanghai. Low oxygen levels in tumors mean that the body’s immune cells often cannot survive long enough to kill cancer cells (SN: 02/22/17). Hypoxic cells are also resistant to treatments like radiation and even traditional chemotherapies because there isn’t enough blood flow to deliver a lethal dose, says Fan Zhang of Fudan, who studies biomedical materials.

“On the other hand, it provides a target for precision tumor treatment,” Xia and Zhang write in the new paper.

Hypoxia could act as a beacon for chemicals called hypoxia-activated prodrugs. These are chemotherapy drugs that have a bonding chemical that ensures the drug only becomes active in a low-oxygen environment, says Qing Zhang, a molecular biologist at the University of Texas Southwestern Medical Center in Dallas, who has no not participated in the study.

But hypoxia-activated prodrugs don’t show much benefit in clinical trials, perhaps in part because the solid tumors they’re deployed against aren’t uniformly hypoxic or not hypoxic enough. Xia and Fan Zhang wanted to find a way to make tumors more hypoxic, to give prodrugs a better chance.

The researchers and their colleagues therefore deployed a tiny, flexible battery that could partially wrap around a tumor. The battery’s zinc electrode charges itself by drawing in oxygen from the environment. It also creates highly reactive oxygen pairs that can damage DNA but are not a usable form of oxygen for cells.

By absorbing most of the available oxygen and producing many pairs of reactive oxygen, the battery alone was able to shrink tumors in mice up to 26% of their original size two weeks after implantation . When combined with a hypoxia-activated prodrug, the average tumor size decreased by 90%.

“I think the concept, the scientific basis, is solid,” says Qing Zhang. The results are encouraging, he says, but extremely preliminary. Not only have the batteries been deployed only in mice, but they have also been used against mouse-specific breast cancer. “It needs to be tested in multiple models of breast cancer, and needs to be tested in other cancer models as well,” he says. And, of course, in humans.

And a 90% decrease in tumor size is not a 100% decrease. “There’s still 10% left,” says Qing Zhang. If these cells survive, it could mean that they are resistant to hypoxia and the tumor could grow back. As with many treatments, he says, it will likely need to be combined with other therapies to ensure the entire tumor is zapped for good.

Xia, Fan Zhang and their colleagues are already considering how the battery might need to be made more flexible and powerful to work on human-sized tumors – using battery power to starve the cancer of air.