Enhanced Neuromodulation Using PC-CNTs and NIR Photothermal Therapy for Preventing Ventricular Arrhythmias.

BACKGROUND

Cardiac sympathetic hyperactivation of the left stellate ganglion (LSG) critically promotes ventricular arrhythmias (VAs) following myocardial infarction (MI). Although neuromodulatory strategies targeting sympathetic activity have shown therapeutic potential, current strategies are limited by invasiveness, incomplete targeting and transient efficacy. Therefore, safe and precise approaches for modulating LSG activity are needed. This study aimed to investigate the enhanced neuromodulatory effects of phospholipid-coated carbon nanotubes (PC-CNTs) combined with near-infrared (NIR) photothermal therapy on the LSG for preventing post-MI VAs.

METHODS

PC-CNTs were synthesized and characterized, followed by evaluation of their photothermal properties and in vitro/in vivo biocompatibility. In a canine MI model induced by left anterior descending artery occlusion (n = 18), animals were randomly assigned to PBS, PC-CNTs and PC-CNTs + NIR groups. PBS or PC-CNTs (30 μg mL-1, 0.1 mL) were locally microinjected into the LSG, and animals in the PC-CNTs + NIR group subsequently received 808 nm NIR laser irradiation (1.0 W cm-2 for 5 min). LSG neural activity, heart rate variability (HRV), ventricular effective refractory period (ERP) and VA incidence were assessed. Transcriptomic profiling of LSG tissue and molecular analysis of peri-ganglionic adipose tissue were performed to evaluate therapeutic effects and potential mechanisms.

RESULTS

PC-CNTs exhibited excellent photothermal conversion efficiency and favorable biocompatibility. In vivo, PC-CNTs treatment suppressed MI-induced LSG hyperactivity, improved cardiac autonomic balance, enhanced ventricular electrophysiological stability and reduced VA susceptibility compared with the PBS group. The addition of NIR photothermal therapy further enhanced these protective effects, resulting in further suppression of sympathetic activation and reduction of post-MI arrhythmias. Molecular analyses suggested that combined PC-CNTs and NIR treatment modulated the LSG microenvironment, as evidenced by reduced expression of inflammation-related genes (CXCL14, CSF3, TIMP1 and CRLF1), indicating attenuation of neuroinflammatory signaling. Additionally, NIR-induced local hyperthermia was associated with thermogenic browning of peri-ganglionic white adipose tissue, characterized by increased expression of thermogenic markers and reduced adipocyte size. These changes may contribute to reduced sympathetic hyperactivity and decreased arrhythmia susceptibility.

CONCLUSION

The combination of PC-CNTs and NIR photothermal therapy provides enhanced anti-arrhythmic effects associated with suppression of LSG hyperactivity and modulation of neuroinflammatory signaling and peri-ganglionic adipose browning, representing a promising preclinical strategy for preventing VAs.