Sequestered in immune cells, barium titanate nanoparticles stimulated by ultrasound launch inflammatory response

Chestnut Hill, Mass (1/14/2026) – Piezoelectric nanoparticles deployed inside immune cells and stimulated remotely by ultrasound can trigger the body’s disease-fighting response, an interdisciplinary team of Boston College researchers recently reported in the journal Scientific Reports.

The use of piezoelectric particles to activate macrophages, cells central to the body’s immune response, could potentially allow for the precise, on-demand activation of cells specifically at an infection or tumor site, avoiding the toxicity and side effects associated with systemic administration of drugs, according to the co-authors of the study.

“We wanted to find out if we can we use physics, in the forms of piezoelectricity and ultrasound, to control biology – by directing differentiation of immune cells – in such a way as to control inflammation and, in a broader sense, discover how cells coherently respond to a diverse set of biophysical stimuli” said Boston College Ferris Professor of Physics Michael J. Naughton, a co-author of the report.

Piezoelectric materials generate an electric charge when subjected to mechanical stress, such as by ultrasound, and they can also deform when an electric field is applied. Common examples include certain crystals, ceramics, and biological materials such as bone and DNA. In this case, the researchers used barium titanate.

The team used the nanoparticles to study mammalian macrophage cells, which are particularly sensitive to biological and biophysical stimuli, according to the report, titled “Barium titanate piezoelectric nanoparticles induce M1 polarization in mouse macrophages via ultrasound in vitro”.

The immune cells that had taken up the nanoparticles and were subjected to the bioelectric effect of ultrasound became activated to a form that can fight infection, attack tumors, and potentially enhance current therapeutic approaches, according to the report.

The researchers also made a surprising discovery.

“We found that too high an ultrasound power could kill nanoparticle-loaded cells, so we lowered the power to avoid this,” said Naughton.  “Upon second thought, we realized that we could kill cells by deploying this method. This led us to think: what about cancer?”

The team began testing the nanoparticle plus ultrasound method as a therapy against cancer. Since then, they have obtained funding from the Mathers Foundation to develop the method as a cancer-fighting therapy, said Naughton.

The team is collaborating with Yale School of Medicine researchers, who have added a radioactive "tag" to the nanoparticles so they can be tracked inside cancer cells via PET imaging, Naughton said. That could potentially find use as a focused ultrasound cancer therapy that combines diagnostic imaging and therapeutic treatment at the same time.

Immune cells are particularly responsive to biophysical as well as biochemical cues. So an important next-step is to understand how cells respond to such cues, said Connolly.

“With what we have learned, we suggest that biophysical regulation of immune cells involves the  formation of little droplets inside the cells that sequester certain genes and support key cellular activities, ultimately controlling genes essential to life,” Boston College Research Professor of Biology Timothy Connolly, also a co-author of the study. “If so, this could represent a new, universal biophysical code of biology.”

Such a code could help to explain how biological cells coherently respond to a wide range of physical or environmental conditions that influence a diverse set of cellular phenotypes, from cancer and aging to immune cell activation, Connolly added.

To investigate this, the team plans to undertake single cell genetic sequencing to look for commonality between biophysically- and biologically-regulated cells.

In addition to Naughton and Connolly, co-authors of the report included Professor of Physics Krzysztof Kempa, and BC undergraduate seniors Camille Johnson, and Allison Chen, and Dylan Hatt, a 2024 BC graduate.