# Remote Activation of Spinal TRPV1 by Magnetic Nanocubes Confers Cardioprotection Against Myocardial Ischemia‐Reperfusion Injury

## TL;DR

Researchers developed magnetic nanocubes that activate spinal TRPV1 channels to protect the heart from injury during ischemia and reperfusion.

## Contribution

A novel non-invasive neuromodulation therapy using magnetic nanocubes to target spinal TRPV1 for cardioprotection.

## Key findings

- FeNCs-TRPV1 specifically activate TRPV1 channels and trigger Ca2+ influx under an alternating current magnetic field.
- Intraspinally injected FeNCs-TRPV1 reduce cardiac injury and ventricular arrhythmia during myocardial ischemia and reperfusion.
- The therapy enhances cardiac cell survival by inhibiting apoptosis and reducing neuropeptide release.

## Abstract

The heat‐sensitive transient receptor potential vanilloid 1 (TRPV1), which is highly expressed on cardiac sensory neurons, reportedly plays a crucial role in transmitting nociceptive signals from the heart to the spinal cord during myocardial ischemia and reperfusion. Here, iron oxide nanocubes (FeNCs) are developed that are conjugated with an antibody against the extracellular portion of TRPV1, and they are named FeNCs‐TRPV1. In F11 cell line and primary dorsal root ganglion neurons, FeNCs‐TRPV1 specifically activate TRPV1 channels and trigger Ca2+ influx through magnetothermal effect under an alternating current magnetic field (ACMF). Intraspinally injected FeNCs‐TRPV1 induced TRPV1 desensitization in rats exposed to repetitive and transient ACMF before ischemia, resulting in the inhibition of TRPV1‐mediated Ca2+ signaling and neuropeptide release in the spinal cord during myocardial ischemia and reperfusion. Consequently, FeNCs‐TRPV1 reduce cardiac injury and ventricular arrhythmia, enhance the activity of prosurvival kinases, and inhibit myocardial cell apoptosis. These findings suggest that magnetic nanomaterials‐mediated remote regulation of spinal TRPV1 can be a novel non‐invasive neuromodulation therapy for the treatment of myocardial ischemia‐reperfusion (IR) injury.

Fe‐based magnetic nanocubes conjugated with TRPV1 antibodies (FeNCs‐TRPV1) are developed for the specific targeting of TRPV1 channels. Intraspinally injected FeNCs‐TRPV1 induces TRPV1 desensitization in rats exposed to repetitive and transient ACMF. This results in a significant reduction of myocardial ischemic injury, and the cardioprotection is associated with reduced neuropeptides release, decreased cardiac sympathetic efferent activity, and enhanced cardiac cell survival.