Seeing the sound : materials-enabled deep-tissue light delivery and neuromodulation
Keywords: Engineering.
Materials Science and Engineering.

The application of light in biological research has significantly enhanced our understanding of the complex processes within living organisms, resulting in a multitude of breakthroughs and advancements in fields such as medicine and biotechnology. However, one significant challenge that limits the utility of light in vivo lies in the strong absorption and scattering of photons by the biological tissues, which prevent efficient and precise light delivery deep into the body. To address this challenge, we developed acoustic and optical bio-interfaces that can non-invasively deliver photons deep inside the tissue for various applications. First, we synthesized multi-color mechanoluminescent (ML) colloids as ultrasound-mediated nanoscopic light sources using a biomineral-inspired suppressed dissolution approach. This synthesis approach utilizes a unique phenomenon of suppressed dissolution observed in Nature, and can produce ML colloids down to 20 nm from their micro-sized precursors while preserving the optical properties. The produced ML colloids can be systemically delivered into the blood stream, and produce transient and localized light emission upon the stimulation of deep-penetrating focused ultrasound (FUS). We demonstrated that the ultrasound-mediated light emission can activate channelrhodopsin-2 (ChR2)-expressing neurons in the mouse brain, producing significant behavioral and histological changes. The use of an acoustic interface eliminates any brain implants or scalp incision, thus allowing non-invasive neuromodulation. Second, using a similar synthesis strategy, we produced multi-color persistent luminescence (PerL) colloids as circulation-delivered light sources. These PerL colloids can store photoexcitation energy in the lattice, and gradually release it as light in an extended period of time. We showed that these PerL colloids are among the brightest afterglow materials ever reported, with short emission wavelengths desired for activating light-sensitive proteins. We then demonstrated the utility of these PerL colloids in excitation-free imaging of brain vasculatures after systemic delivery, and used them as internal light sources to excite endogenously expressed fluorescent proteins in the mouse brain. Third, we developed an optical neuromodulation technique in the second near-infrared window (NIR-II, 1000−1700 nm) using semiconducting polymer nanotransducers with bandgap engineering. After local delivery into the brain, these nanotransducers strongly absorb brain-penetrant NIR-II light and efficiently convert it into heat, which can then activate ectopically expressed temperature sensitive ion channels for neuromodulation. We demonstrated the utility of this NIR-II neuromodulation technique in the motor cortex, hippocampus, and ventral tegmental area (VTA) of mice, producing significant behavioral, histological, and electrophysiological changes. The use of an NIR-II interface allows complete elimination of invasive brain implants and head tethering, which will be advantageous for the future study of social interactions in rodents