Phospholipid-Coated Carbon Nanotubes as Neuromodulators to Protect against Ventricular Arrhythmias

Left stellate ganglion (LSG) hyperactivity is a critical factor in ventricular arrhythmias (VAs), and inhibiting LSG activity remains challenging. Carbon nanotubes (CNTs) are gaining popularity as promising nanomedicines for applications in neuromodulation owing to their exceptional physicochemical properties and capacity to interface with neurons and neuronal circuits. We have fabricated multiwalled CNTs coated with 1,2-diphytanoyl-sn-glycero-3-phosphocholine (PC-CNTs) and explored their neuromodulatory effects in protection against VAs. In vitro calcium imaging of HT22 cells demonstrates that PC-CNTs effectively inhibit neuronal activity. In vivo, PC-CNTs are microinjected into the canine LSG in a model of myocardial ischemia. PC-CNTs significantly inhibit LSG neural activity and function, suppress sympathetic nerve indices of heart rate variability, and mitigate myocardial ischemia-induced VAs. Histological analysis of the LSG reveals that PC-CNTs downregulate the levels of c-fos and nerve growth factor. Transcriptomic analysis of the LSG indicates that attenuating neuroinflammation might be the underlying mechanism of the therapeutic effects of PC-CNTs. This study provides compelling evidence that PC-CNTs are potential therapeutic neuromodulators, representing a promising approach to protecting against VAs.