Researchers have developed a novel method for delivering fluorescent sensors across the blood-brain barrier (BBB) to monitor
Successful Sensor Delivery Using Exosomes
The BBB laboratory model consisted of a layer of endothelial cells on top of a solution containing brain cells. The researchers’ sensor-loaded exosomes were nearly four times more efficient than conventional sensor delivery systems at passing through the endothelial barrier and releasing the fluorescent sensor into the brain cells. This was confirmed by measuring the observed level of ATP-binding-induced fluorescence. Next, Lu’s team injected mouse models of Alzheimer’s disease with either the sensor-loaded exosomes or free-floating unloaded sensors. By measuring fluorescence signals in the mice, the researchers found that the free-floating sensors stayed mainly in the blood, liver, kidneys, and lungs, while sensors delivered via exosomes accumulated in the brain.
Promising Results in Alzheimer’s Mouse Models
In mouse models of Alzheimer’s disease, the exosome-delivered sensors identified the location and concentration of ATP in different regions of the brain. Specifically, they observed low levels of ATP in the hippocampus, cortex, and subiculum regions of the brain, which are indicative of the disease. The researchers say that their exosome-loaded ATP-reactive sensors show promise for non-invasive live brain imaging and could be developed further to create sensors for a range of clinically relevant neurotransmitters.
Reference: “Delivering DNA Aptamers Across the Blood−Brain Barrier Reveals Heterogeneous Decreased ATP in Different Brain Regions of Alzheimer’s Disease Mouse Models, 31 July 2024, ACS Central Science.
DOI: 10.1021/acscentsci.4c00563
The authors acknowledge funding from the U.S.