CB1-Antibody Modified Liposomes for Targeted Modulation of Epileptiform Activities Synchronously Detected by Microelectrode Arrays

摘要

Temporal lobe epilepsy (TLE) is a focal, recurrent, and refractory neurological disorder. Therefore, precisely targeted treatments for TLE are greatly needed. We designed anti-CB1 liposomes that can bind to CB1 receptors in the hippocampus to deliver photocaged compounds (ruthenium bipyridine triphenylphosphine gamma-aminobutyric acid, RuBi-GABA) in the TLE rats. A 16-channel silicon microelectrode array (MEA) was implanted for simultaneously monitoring electrophysiological signals of neurons. The results showed that anti-CB1 liposomes were larger in size and remained in the hippocampus longer than unmodified liposomes. Following the blue light stimulation, the neural firing rates and the local field potentials of hippocampal neurons were significantly reduced. It is indicated that RuBi-GABA was enriched near hippocampal neurons due to anti-CB1 liposome delivery and photolyzed by optical stimulation, resulting dissociation of GABA to exert inhibitory actions. Furthermore, K-means cluster analysis revealed that the firing rates of interneurons were decreased to a greater extent than those of pyramidal neurons, which may have been a result of the uneven diffusion of RuBi-GABA due to liposomes binding to CB1. In this study, we developed a novel, targeted method to regulate neural electrophysiology in the hippocampus of the TLE rat using antibody-modified nanoliposomes, implantable MEA, and photocaged compounds. This method effectively suppressed hippocampal activities during seizure ictus with high spatiotemporal resolution, which is a crucial exploration of targeted therapy for epilepsy.