Top: The sub-retinal implantation of Au-nanoparticle-decorated TiO2 nanowires, serving the function of artificial photoreceptors in a retina. Bottom: Raster plots and post stimulus time histograms of spikes from V1 neurons in blind mice (left), NW arrays-implanted blind mice two days after implantation (middle left), two months after implantation (middle), five months after implantation (middle right), and wild-type mice (right). The purple shade area indicates the presentation of light.
A false-colored scanning electron microscope image of the interface between a single coaxial silicon nanowire (green) and a neuron cell (blue). (Credit: Ramya Parameswaran, University of Chicago.)Two independent studies demonstrate how nanowires could help restore impaired neurological functions involved in vision and movement.
In one study, researchers at Fudan University and the University of Science and Technology of China in Hefei, developed titania nanowires coated with gold nanoparticles to act as artificial photoreceptors, restoring visual function in blind mice [Tang et al., Nature Communications 9 (2018) 786, https://doi.org/10.1038/ s41467-018-03212-0].
Degenerative diseases such as retinitis pigmentosa and macular degeneration result in damage to the light-sensitive tissue of the retina, which transforms light information into neural signals in the brain. Loss or damage to photoreceptors in the retina impair vision or result in complete blindness.
Light-responsive artificial photoreceptors acting as a replacement interface between the eye and the brain offer the exciting prospect of restoring some sort of light sensitivity or vision to blind patients. Arrays of one-dimensional nanowires are a promising candidate, not least because of their resemblance to the architecture and morphology of rod and cone photoreceptors.
Jiayi Zhang and Gengfeng Zheng, and their colleagues, fabricated arrays of Au-nanoparticle-decorated TiO2 nanowires on conducting, flexible fluorine-doped tin oxide or polymer substrates. The nanowires combine a large surface area and high charge transport mobility for efficient photoabsorption and charge separation with excellent biocompatibility. When the semiconducting nanowires arrays are exposed to light, photons are absorbed, generating a voltage that is sufficient to excite nearby neurons (Fig. 1). In this way, the artificial photoreceptors can trigger neurons’ response to light without the need for external wires or power sources.
“Our photoresponsive nanowire array, which can be implanted into the position of impaired photoreceptor cells of a retina, functions as an artificial photoreceptor to relay light information to the rest of the retina and our brain, restoring vision,” explain Zhang and Zheng, who led the effort.
To demonstrate the potential of the approach, the researchers implanted blind mice with the artificial photoreceptor material. Over a two-month test period, during which the material appeared to be stable and biocompatible, the team recorded strong retinal responses to green, blue, and near ultraviolet (UV) light.
“After implantation, not only was the photoresponse of photoreceptor-degenerative retinas recovered, but also the light sensitivity of mice was regenerated, such as pupil dilation,” add the researchers.
Zhang and Zheng believe that their approach is much simpler than alternative strategies requiring power supplies and video cameras to project images onto artificial photoreceptors.
“Our findings open up new possibilities for clinical treatment of blindness from retinitis pigmentosa or age-related macular degeneration,” they say.
The researchers are now working to increase the sensitivity of the material to boost spatial resolution, as well as exploring its longterm biocompatibility. Meanwhile, a team from the University of Chicago has used individual silicon nanowires to stimulate neurons in response to light [Parameswaran et al., Nature Nanotechnology (2018), doi: https:// doi.org/10.1038/s41565-017-0041-7].
Instead of fabricating arrays of nanowires, the team led by Francisco Bezanilla and Bozhi Tian created free-standing, core-shell structure nanowires with a boron-doped, p-type core and a phosphorus-doped, n-type shell. Since the nanowires are grown using a sequential growth process with gold nanoparticles as the catalyst, gold accumulates at grain boundaries and on the surface of the Si structures. When the nanowires are illuminated, the core-shell junction separates the light-generated electrons and holes. Electrons become trapped at the nanowire surface by the gold, where they produce a current in response to the surrounding electrolyte solution in biological conditions. The current is sufficient to trigger a response (via membrane depolarization) in nearby neurons (Fig. 2).
“Our work is unique in that it is a demonstration of a nanotechnology that uses concepts from energy science (photoelectrochemical cells) to excite single neurons in an optical, non-invasive manner, as these nanowires function extracellularly,” explains Tian.
The team demonstrated the effect by simply adding Si nanowires to ganglion neurons cultured from rats. Laser pulses stimulate the neurons only when the nanowires are present and appear to do so in a way physiologically identical to conventional means of injecting current via external electrodes.
“Our material can be dispersed in a non-invasive, drug-like fashion and chemically functionalized to bind specific types of target cells, making it an attractive tool for use in both fundamental bioelectric studies as well as in vivo for therapeutics,” points out Tian.
The degradability of Si in vivo, as well as its ability to absorb light in the near-infrared (NIR) part of the spectrum, which can penetrate deep into tissue, could be advantageous for clinical applications. The nanowires could be injected to target peripheral nerves directly and stimulated remotely using NIR radiation.
“The nanowires are an optimal candidate for non-invasive treatment of diseases involving aberrant electrical activity, such as those involving peripheral nerve damage, psychiatric disorders, and Parkinson’s disease,” says Ramya Parameswaran, lead author of the study.
Currently, the greatest obstacle to the development of this approach is the need for high-power laser illumination to activate the nanowires. But the researchers are now undertaking further studies to improve the stimulation efficiency.
Charles M. Lieber of Harvard University believes that the results demonstrate two new, distinct, and exciting applications of nanowires for controlling the behavior of neurons. On one hand, Tian and Bezanilla’s approach shows how freestanding Si nanowire structures can serve as ‘wireless’ non-genetic devices for optically exciting neurons.
“The work is creative, intellectually-deep and opens up a new avenue of nano-bio research with immediate opportunities for extending fundamental capabilities for neuroscience as new a novel tool,” he says.
On the other hand, Zhang and Zheng have taken advantage of the unique geometry of vertically grown nanowires to restore visual response in blind mice.
“Excitingly, this opens the door for a new type of sub-retinal implant that can already be applied to and developed further in rodents and ultimately will be interesting to consider as prosthetic devices for vision restoration in humans,” suggests Lieber.
This article was first published in Nano Today 20 (2018) 1-6.