Nanoliposome-encapsulated caged-GABA for modulating neural electrophysiological activity with simultaneous detection by microelectrode arrays

Effective and precise neural modulation with real-time detection in the brain is of great importance and represents a significant challenge. Nanoliposome-encapsulated light-sensitive compounds have excellent characteristics such as high temporal and spatial resolution, delayed drug clearance, and restricted drug biodistribution for neural modulation. In this study, we developed a nanoliposome-based delivery system for ruthenium-based caged GABA compounds (Nanolipo-Ru) to modulate neural activity and allow for real-time monitoring using the microelectrode arrays (MEAs). The Nanolipo-Ru nanoparticles had an average size of 134.10 ± 4.30 nm and exhibited excellent stability for seven weeks. For the in vivo experiment in the rat, release of GABA by Nanolipo-Ru under blue light illumination resulted in an average firing rate reduction in interneurons and pyramidal neurons in the same brain region of 79.4% and 81.6%, respectively. Simultaneously, the average power of local field potentials in the 0-15 Hz range degraded from 4.34 to 0.85 mW. In addition, the Nanolipo-Ru nanoparticles have the potential to provide more flexible timing of modulation than unencapsulated RuBi-GABA in the experiments. These results indicated that Nanolipo-Ru could be an effective platform for regulating neuronal electrophysiology. Furthermore, nanoliposomes with appropriate modifications would render promising utilities for targeting of specific types of neurons in the future.