Nanomachine-Based Flexible Bubbles for Alleviating Long QT Syndrome.

Abstract

Typically occurring in individuals with a genetic predisposition, long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization (QT interval prolongation) and susceptibility to tip torsion, ventricular tachycardia, ventricular fibrillation, and sudden cardiac death. Currently, treatment options for LQTS include medication and surgery, but these may cause patient discomfort and disease recurrence. In this study, using biocompatible carrier-free nanomachine-based flexible bubbles are proposed to deliver phycocyanin (PC) for heart protection associated with electrophysiological stability in LQTS in vivo in mice. To form the structures, l-arginine (L-Arg) is polymerized with PC through electrostatic interactions, and Au is sputtered onto one side of the surface of L-arg/PC, functioning as a trigger for generating nitric oxide (NO) in the in vivo microenvironment. The asymmetrically released NO cargo provided a means of improving heart function and arrhythmia by delivering PC, and acted as a propellant for transporting the nanomachine to the target site. After accumulating at the site of heart damage, the nanomachines are triggered by reactive oxygen species (ROS). The accumulated nanomachines provided considerable diffusion of PC, which attenuated heart damage. The nanomachines, with ROS-induced targeting and delivery of PC, have immense potential for providing heart protection by modulating myocardial gap junction proteins and the hypoxic environment, and by ameliorating electrical remodeling in LQTS, and therefore may support future clinical testing.