Stanford researchers have found a way to use ultrasound and nanoparticles to generate light deep inside the body without surgery or implants. The proof-of-concept in mice could transform how doctors stimulate neurons, treat cancer and control gene editing in the future.
For decades, doctors and scientists have wanted the power to shine light deep inside the body without surgery. Now, Stanford researchers say they have a promising new way to do it — by turning ultrasound waves into tiny, precise points of light anywhere blood can flow.
The team has developed a noninvasive technique that uses nanoparticles circulating in the bloodstream to convert focused ultrasound into light inside living tissue. In mice, they showed they could light up specific spots in the brain and even steer behavior, all without implants or cutting into the skull.
The work, published April 13 in Nature Materials, could eventually make a range of light-based therapies safer and easier, from brain stimulation to cancer treatment and even gene editing.
Light is already a powerful tool in biology and medicine. It can be used to activate neurons, guide tissue growth and trigger drugs that kill cancer cells. But light does not travel well through tissue, which is why most current methods rely on invasive procedures such as inserting optical fibers or removing bone.
Ultrasound, by contrast, can pass through skin, bone and organs and is already widely used in clinics for imaging. That makes it an attractive carrier for reaching deep targets.
“Ultrasound is very convenient to use, and it penetrates much deeper into the body than light,” senior author Guosong Hong, an assistant professor of materials science and engineering in Stanford’s School of Engineering and faculty scholar at the Wu Tsai Neurosciences Institute, said in a news release.
The key to the new approach is a special class of ceramic materials that emit light when they are mechanically stressed — for example, when squeezed or vibrated. These materials are more commonly found in building applications than in medicine, but Hong’s group reimagined them as tiny internal light sources.
The researchers first ground the ceramics down into nanoparticles and coated them with a biocompatible layer so they could be suspended in a liquid and safely injected into the bloodstream. Once injected into mice, the particles traveled through blood vessels to tissues throughout the body.
“Wherever there is live soft tissue, there’s going to be vasculature providing nutrients, oxygen, and blood cells. We can also use that to deliver light,” Hong added.
On their own, the nanoparticles remain essentially dark. But when the scientists aim focused ultrasound at a particular spot in the body, the sound waves jostle the particles there, causing them to emit blue light with a wavelength of 490 nanometers.
By moving the ultrasound focus, the team can scan through tissue and “paint” light in different locations, even creating multiple lit spots at once. Because the ultrasound can be tightly focused, the resulting light is generated only where it is needed.
To prove the light was truly being produced deep inside the body — not just near the surface — the researchers built a tiny ultrasound “hat” for mice. Placed on the animals’ heads, the device allowed them to direct ultrasound to different regions of the brain while the mice moved freely.
When the light-sensitive neurons in those brain regions were activated by the internally generated light, the mice turned left or right depending on which area was stimulated. That experiment showed that the ultrasound-triggered light was strong and precise enough to control neural circuits.
“We can noninvasively tune this emission in different brain regions to produce a variety of behavioral outcomes,” added Hong. “This is a general method that can enable any application that requires light in deep tissue.”
The current nanoparticles emit blue light, which is useful for exciting many types of neurons and for a cancer treatment approach known as photodynamic therapy, where light activates drugs that destroy tumor cells. But the same strategy could be adapted to other colors of light by swapping in different nanomaterials.
Hong and his colleagues are already testing materials that emit ultraviolet light, which can kill bacteria and viruses. In principle, other wavelengths could be chosen to match specific medical tasks, such as activating particular drugs or sensors.
The team is also collaborating with Michael Lin, a professor of neurobiology and of bioengineering in the schools of Engineering and Medicine, to pair the light-producing system with gene-editing tools that are controlled by light. One of the major challenges in gene editing is avoiding unwanted changes in the wrong cells. If the editing machinery can be switched on only where ultrasound is focused, it might be possible to sharply limit where edits occur.
Before any of these ideas can move toward human use, safety will be a central question. The ceramic nanoparticles used in the study did not appear to cause problems in mice, but they do not break down quickly and could build up in organs such as the liver over time.
The next step, according to Hong, is to replace the ceramic particles with materials that the body can safely degrade and clear, while preserving the ability to turn ultrasound into light.
“What we’re demonstrating here is a proof of concept showing that you can produce light emission in a programmable manner deep within the body,” he said. “If we can replace the material with one that is safer to be used in humans, that will start to pave the way for clinical applications.”
The research brings together expertise from materials science, neuroscience, bioengineering and medicine at Stanford, along with collaborators at the University of Virginia and the University of Southern California. It also builds on a broader push in the field to find noninvasive ways to reach and control cells deep inside the body.
If the approach can be made safe and tuned for human use, future doctors might one day use an ultrasound probe not just to see inside the body, but to switch on therapies with pinpoint accuracy — lighting up only the cells that need to respond, and leaving the rest in the dark.
Source: Stanford University