Professor Tao Sun is harnessing macrophages’ appetite for cellular trash to find tumors and diseased cells in the brain and, with help from tiny excited bubbles, alert other immune cells to the fight.
Researchers at Northeastern University are using ultrasound to pair voracious debris-clearing blood cells with microscopic bubbles to control the immune system’s response to disease in the brain and beyond.
Focused on ultra-hungry white blood cells called macrophages, assistant professor of biological engineering Tao Sun is harnessing the macrophage’s appetite for cellular trash to find tumors and diseased cells in the body and, with help from tiny excited bubbles, alert other immune cells to the fight.
“Scientists like to use the word ‘plastic’ to describe macrophages,” says Sun. “They change their behaviors all the time. They can be big fighters. They can also be resting, doing nothing, like a couch potato.”
This very changeability, Sun says, makes macrophages potent tools in the fight against cancer and other inflammation associated diseases. Sun’s most recent work, funded with $1.99 million through a Maximizing Investigators’ Research Award from the National Institutes of Health, is studying ways to inject tiny bubbles into the bloodstream and, after the bubbles latch on to macrophages, use ultrasound waves to control the bubbles.
Since ultrasound waves create real-time images, scientists will be able to see what’s happening inside the macrophage — an imaging breakthrough — and remotely change macrophage behavior. They can also track the cells as they move through the body.
Macrophages and their precursors, monocytes, work throughout the bloodstream and tissues to regulate immune defense and inflammation, Sun says. But this research is ultimately focused on their presence in the brain and how they travel there. As delicate as it is, the human brain is protected by specialized endothelial cells — a blood-brain barrier — to keep toxins out.
When macrophages are active, they fight inflammation, eating cancer cells and recruiting other immune cells. But their inactive state, Sun says, is an anti-inflammatory “healing” state. This condition actually helps cancer cells grow.
By blasting ultrasound waves at the brain, he says, scientists will be able to make the bubbles vibrate and expand briefly. This movement reverberates, causing the bubbles to expand briefly and weaken the blood-brain barrier. With the newly developed bubble-carrying macrophages and ultrasound-opened blood-brain barrier, the external trigger may switch the macrophage state back to a cancer-fighting inflammatory state.
“With these living cell probes we can actually use ultrasound waves externally to control biological function,” Sun says. Switching macrophages to their inflammatory state creates a hostile environment for cancer, he says, but a conducive one for treatment.
“The first step is actually changing from the anti-inflammatory, the bad healing state, and turning it into the pro-inflammatory state, the best for fighting cancer,” he says. The next step, he says, would be to pair this method with drugs.
“When we have ultrasound as external energy, we don’t really need surgery,” Sun says. “When you send ultrasound waves directly into the brain they provide spatial targeting to specific places inside the brain, whether there’s a tumor or other pathology related to Alzheimer’s or Parkinson’s.”