Engineering nucleic acid functional probes in neuroimaging

Functional imaging of the brain gives us increasingly detailed information about the location of nervous activity. Imaging probes are therefore in demand to target and visualize the neurological processes. However, the deep location of the brain and the blood-brain barrier (BBB) poses challenges in signal detection and probe delivery to the brain. In recent years, nucleic acid imaging probes have been a research frontline to cope with these challenges. Nucleic acid probes showed advantages in preparation, functionalization, targeting and BBB-penetrating. This review will focus on nucleic acid probes-based neuroimaging. In the beginning, common categories of nucleic acid imaging probes are introduced with the targeting strategies. In the next part, we focus on recent advances in strategies of deep tissue imaging in situ and delivery across the blood-brain barrier (BBB). In addition, the perspective on the advantages, limitations and potential development of neural nucleic acid functional imaging probes are elaborated. • Nucleic acids-based probes have realized the specific and smart imaging for the targets or process in neuroscience. • The engineered nucleic acid probes could pass through the blood-brain barrier efficiently and achieve internal tissue imaging. • Nucleic acids served as a powerful imaging platform for imaging different targets in neuroscience in different ways.