Date: 21st May 2021
Worldwide, over 13 million people have a stroke each year and as the second leading of cause of death, around 5.5 million people will die as a result. The most common cause is a blood vessel blockage in the brain, and for those that survive, millions experience disability. This is due to a lack of blood supply, causing a disruption of oxygen and nutrients to the brain cells. Now, researchers have used a near-infrared light (NIR)-driven nano-photosynthesis biosystem capable of generating oxygen and absorbing carbon dioxide, to rescue neurons from ischemia in an effort towards treating strokes.
An ischaemic stroke is the most common type of stroke which is caused by a blood vessel blockage in the brain. For ischaemic stroke or transient ischaemic attack, medication and/or surgery is traditionally recommended, as removing the clot as soon as possible is crucial in minimising the damage to the brain. However, these options are not without risk and are time dependent – with only a narrow window of opportunity existing.
Now, researchers at Huazhong University of Science and Technology, China, led by Lin Wang, Zheng Wang, Guobin Wang have paired the blue-green algae, Synechococcus elongatus, with upconversion nanoparticles – which can convert low energy photons into high energy photons – activating photosynthesis in the microbes which reduced the number of dying neurons after a stroke, and facilitated improved motor function recovery upon exposure to near-infrared light.
Blue-green algae, has previously been explored as a potential treatment for lack of oxygen in heart tissue and tumours, harnessing the power of photosynthesis that converts light energy into chemical energy – using carbon dioxide and releasing oxygen. However, photosynthesis requires visible light (high energy photons) to be triggered, and penetration of this light into the brain is stopped by the skull. Near-infrared light (low energy photons) can pass through however, it is insufficient to directly power this chemical reaction.
To overcome these limitations the team have harnessed upconverting nanoparticles (UPNPs), these are an emerging type of fluorophore that exhibit photon upconversion. Here, two or more incident photons of relatively low energy are absorbed and converted into one emitted photon with higher energy – turning near-infrared light into visible light.
To start the team tested the nano-photosynthesis approach in a cell study using neuroblastoma and microglial cell lines. They showed a reduction in the number of neurons that died post oxygen and glucose deprivation indicating the therapy could translate into a promising treatment for oxygen starvation in the brain – consuming the accumulated carbon dioxide and simultaneously producing oxygen.
To determine the potential therapeutic strategy for patients with strokes, the team cerebrally delivered the microbes along with the UPNPs into mice with a blocked cerebral artery and then exposed the animals to an external source of near-infrared light.
They found the therapy enhanced angiogenesis, reduced the numbers of dying neurons, and was associated with a decrease in infarction size. Post-stroke neurological function was measured using a modified Neurological Severity Score, which reflected the performance of motor, sensory, reflex and balance. Animals receiving the therapy showed significant improvement in motor coordination and limb control, indicating a recovery of dexterity and providing compelling evidence that this nano-biosystem warrants further investigation for the treatment of strokes.
Conclusions and future applications
The team here have successfully demonstrated the potential of a near-infrared light-driven nano-photosynthesis biosystem to generate oxygen in vivo for the treatment of strokes, reducing neuron damage and improving motor function.
This oxygen-generating therapy provides a novel approach for stroke treatment, by harnessing microorganisms and nanotechnology. Although still in its infancy, the proof-of-concept data supports its advancement towards clinical trials, which the researchers will be now be working towards, assessing its safety and efficacy.
The nano-photosynthesis biosystem could provide a valuable alternative therapy for stroke patients, and there is a great unmet clinical need for therapies to halt neuronal damage or to stimulate their repair. Research is beginning to make inroads into developing novel therapies to address this. Recently it was reported that a new glial cell therapy could halt progressive damage caused by white matter strokes and could stimulate the brain’s own repair process, leading to enhanced motor and cognitive recovery. Gene therapy and designer cytokine therapy are also being assessed as a method to regenerate nerves after damage. Whilst, gene and cytokine therapy may provide benefits after the damage or injury has occurred, time to treatment for strokes is crucial.
The biosystem reported here, if applied rapidly after a stroke, could minimise damage in the hope that permanent injury was avoided. One could envisage, this type of oxygen-generating therapy could be used as a short-term treatment for several conditions associated with hypoxia, limiting or slowing immediate cell death, and where necessary increasing therapeutic time windows for other next generation therapies to be administered.
For more information please see the press release from the American Chemical Society
Wang, J., Su, Q., Lv, Q., Cai, B., Xiaohalati, X., Wang, G., Wang, Z., and Wang, L. (2021). Oxygen-Generating Cyanobacteria Powered by Upconversion-Nanoparticles-Converted Near-Infrared Light for Ischemic Stroke Treatment. Nano Letters.
https://doi.org/10.1021/acs.nanolett.1c00719
