Stanford researchers create noninvasive way to deliver light deep inside the body

Light has an increasing number of applications in biology and medicine – it can be used to stimulate cell growth, manipulate neural signals, and treat some cancers – but it doesn't easily pass through tissue. Most methods to bring light deep within the body are invasive, requiring either tissue to be removed or an optical fiber to be inserted.

Researchers at Stanford have created a noninvasive way to deliver light to specific locations anywhere in the body. Their work, published April 13 in Nature Materials, uses nanomaterials distributed through the bloodstream to turn ultrasound waves into precise points of light. The technique provides a potential roadmap for easier, less invasive light-based treatments.

Ultrasound is very convenient to use, and it penetrates much deeper into the body than light. With these materials, we can produce light emission in the brain, in the gut, in the spinal cord, in the muscle – virtually anywhere – without needing a physical implant."

Guosong Hong, assistant professor of materials science and engineering, School of Engineering and senior author on the paper

Light on demand

The light-producing materials that Hong and his colleagues started with are large, ceramic particles more likely to be used in building materials than in the body. These materials give off light in response to mechanical stress, which can be created by ultrasound waves.

The researchers processed them down into nanoparticles and created a biocompatible coating that would allow the particles to be suspended in a solution. Then they injected that solution into mice, where blood vessels carried the nanomaterials to every part of 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 said.

The nanoparticles remain relatively dark until they are hit with focused ultrasound waves. The researchers showed they could create light in multiple locations at a time, as well as use the ultrasound for scanning, creating light as the focal point of the ultrasound moves.

To show that emission was working deeper in the body (since light can't always be seen from the outside), the researchers created a small ultrasound-producing hat for mice, and used it to create light in different parts of a mouse's brain. The light stimulated different neurons, causing the mouse to turn left or right depending on the part of the brain being activated.

"We can noninvasively tune this emission in different brain regions to produce a variety of behavioral outcomes," Hong said. The demonstration showed that light produced from ultrasound can effectively manipulate cell activity within the brain, but there are other potential uses as well. "This is a general method that can enable any application that requires light in deep tissue."

A bright future

The materials used in this work create blue light with a wavelength of 490 nanometers. This wavelength can be used to excite neurons, as the researchers demonstrated, and in photodynamic therapy for cancer. But the same methods could be used to produce other useful wavelengths from different nanomaterials. Hong and his colleagues are currently experimenting with a material that emits ultraviolet light, which can kill bacteria and viruses.

Hong is also working with Michael Lin, a professor of neurobiology and of bioengineering in the schools of Engineering and Medicine, to pair this light-producing method with a gene-editing system. One of the challenges of gene editing is that it can create off-target effects, but by pairing light-producing nanoparticles with a light-activated gene-editing system, the researchers hope to be able to use ultrasound to turn gene editing on and off in localized areas of the body.

Before any of these systems can be used in people, the researchers need to ensure that the nanomaterials are safe. While these materials did not seem to show adverse effects in mice, the researchers noted that they do not break down quickly and have the potential to accumulate in places like the liver. Now that the researchers have demonstrated that ultrasound can be used to produce light, Hong hopes to replace the ceramic nanoparticles with a biological material that will break down safely in the body.

"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," Hong 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."