Reviewed by Lexie CornerAug 1 2024
Researchers at ACS Central Science demonstrate how to package fluorescent sensors for simple passage across the BBB in mice, allowing for better brain imaging.
Researchers demonstrate exosomes loaded with fluorescent sensors that can pass through the blood-brain barrier (BBB), where the sensors light up in the presence of neurotransmitters linked to Alzheimer’s disease in the brain. Image Credit: ACS Central Science 2024, DOI: 10.1021/acscentsci.4c00563
Measuring neurotransmitter levels can determine brain health and identify neurodegenerative diseases like Alzheimer’s. However, because of the blood-brain barrier (BBB), delivering fluorescent sensors that can identify these small molecules to the brain is challenging.
The technique has the potential to improve Alzheimer’s disease detection and therapy with more development.
While a decline in neurotransmitter levels is normal as people age, low adenosine triphosphate (ATP) levels could be a sign of Alzheimer's disease. Researchers have created fluorescent sensors from segments of DNA called aptamers, which light up when they attach to a target molecule. These sensors assess the location and quantity of ATP in the brain.
Methods for transporting these sensors from the circulation to the brain have been devised. However, the majority use synthetic components that cannot easily cross the BBB. Yi Lu and colleagues enclosed an ATP aptamer sensor in exosomes, which are small vesicles produced by brain cells, to create sensors for live brain imaging.
They evaluated the novel sensor delivery technique in BBB lab models as well as Alzheimer’s disease mouse models.
The BBB laboratory model comprised an endothelial cell layer on top of a solution containing brain cells. The researchers developed sensor-loaded exosomes that were roughly four times more effective than traditional sensor delivery systems in getting past the endothelial barrier and releasing the fluorescent sensor into brain cells.
This was validated by determining the observed level of ATP-binding-induced fluorescence. Lu’s team then injected mouse models of Alzheimer’s disease with either sensor-loaded exosomes or free-floating unloaded sensors. By measuring fluorescence signals in the mice, the researchers found that the free-floating sensors remained predominately in the lungs, kidneys, liver, and blood, liver, kidneys, while sensors delivered via exosomes accumulated in the brain.
Exosome-delivered sensors in mouse models of Alzheimer’s disease detected the location and concentration of ATP in several brain regions. They found low amounts of ATP in the hippocampus, cortex, and subiculum areas, indicating the disease.
The researchers believe that their exosome-loaded ATP-reactive sensors have the potential for non-invasive live brain imaging and might be further refined to generate sensors for a variety of clinically important neurotransmitters.
The authors acknowledge the funding from the National Science Foundation Graduate Research Fellowship, the Welch Foundation, the NIH Chemistry-Biology Interface Training Program at the University of Illinois Urbana-Champaign, and the US National Institutes of Health (NIH).
Journal Reference:
Banik, M., et. al. (2024) Delivering DNA Aptamers Across the Blood–Brain Barrier Reveals Heterogeneous Decreased ATP in Different Brain Regions of Alzheimer’s Disease Mouse Models. ACS Central Science. doi:10.1021/acscentsci.4c00563