No mammalian photoreceptor can effectively detect light that exceeds 700 nm, and mammals are unable to see near-infrared (NIR) light or to project a NIR image to the brain. To enable the detection of longer wavelength light in mammals, scientists at the University of Massachusetts Medical School, working with colleagues at the University of Science and Technology of China, developed ocular-injectable photoreceptor-binding upconversion nanoparticles (UCNPs). These nanoparticles, which contain the rare-earth elements erbium and ytterbium, can convert low-energy photons from NIR light into higher-energy green light that mammalian eyes can see. The scientists injected the UCNPs into the eyes of mice. The researchers targeted UCNPs to photoreceptors in mouse eyes by attaching a protein that binds to a sugar molecule on the photoreceptor surface. Then they injected the photoreceptor-binding UCNPs behind the retinas of the mice. Once anchored on the cells, the UCNPs convert NIR into visible, green light. Organic nanoparticles in a vial convert invisible near-infrared light to intense blue light, which can easily be seen by human eyes. Courtesy of Gang Han. To determine whether the injected mice could see and mentally process NIR light, the team conducted several tests. In one test, the researchers placed the mice into a Y-shaped tank of water. One branch of the tank had a platform on which the mice could climb to escape the water. The researchers trained the mice to swim toward visible light in the shape of a triangle, which marked the escape route. A similarly lit circle marked the branch without a platform. Then the researchers replaced the visible light with NIR light. “The mice with the particle injection could see the triangle clearly and swim to it each time, but the mice without the injection could not see or tell the difference between the two shapes,” said professor Gang Han, who is leading the research. The researchers demonstrated that mice injected with these nanoantennas, in addition to perceiving NIR light, could obtain NIR pattern vision and differentiate between sophisticated shape patterns such as triangles and circles. Treated mice were able to perceive these light patterns even in daylight conditions, indicating that the nanoparticles were working in parallel with conventional daylight vision. Because the nanoantennas and photoreceptors were in close proximity to each other, a low-power NIR LED lamp light was sufficient to activate the UCNPs. Although the UCNPs persisted in the mice’s eyes for at least 10 weeks and did not cause any noticeable side effects, Han wants to improve the safety and sensitivity of the nanomaterials before testing them in humans. “The UCNPs in our published paper are inorganic, and there are some drawbacks there,” he said. “The biocompatibility is not completely clear, and we need to improve the brightness of the nanoparticles for human use.” The team is experimenting with UCNPs made up of two organic dyes, instead of rare-earth elements. “We’ve shown that we can make organic UCNPs with much improved brightness compared with the inorganic ones,” Han said. These organic nanoparticles can emit either green or blue light. In addition to having improved properties, the organic dyes could also have fewer regulatory hurdles. One of the next steps for the project might be translating the technology to “man’s best friend.” “If we had a superdog that could see NIR light, we could project a pattern onto a lawbreaker’s body from a distance, and the dog could catch them without disturbing other people,” Han said. The technology could also have important medical applications, such as treating diseases of the eye. “We’re actually looking at how to use NIR light to release a drug from the UNCPs specifically at the photoreceptors,” he said. The research was published in Cell (https://doi.org/10.1016/j.cell.2019.01.038). The research was presented at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition, Aug. 25-29, in San Diego. A study in the journal Cell describes how Gang Han, Ph.D., and colleagues developed technology to give night vision to mammals with an injection that contains nanoantennas, allowing the animals to see light beyond the visual spectrum, into the range of infrared light. Courtesy of UMass Medical School.