Magnetic Field-Responsive Nanodrug to Regulate TRPV1 Pain Receptor

Neuropathic pain is a chronic condition that often requires long-term management, with opioids frequently being the primary option for severe pain relief. Capsaicin, a natural analgesic, holds promise for chronic pain management but is limited by its hydrophobicity, low tissue affinity, and short half-life. In this study, we developed a magnetic field-responsive nanodrug for the on-demand delivery of capsaicin, overcoming these limitations. We utilize iron oxide magnetic nanoparticles (MNPs) functionally coated with thermoresponsive poly(oligo (ethylene glycol) methyl ether methacrylate) (POEGMA). POEGMA nanocoatings on MNPs serve as capsaicin reservoirs. Upon alternating magnetic field (AMFs) exposure, MNPs dissipate heat locally, which triggers the thermodynamic response of their POEGMA nanocoating for capsaicin release. We studied the passive and AMFs-controlled release of capsaicin from MNPs. Then, we investigated the nanodrug for regulating the pain receptor TRPV1, endogenously expressed in primary rat hippocampal neurons, using calcium ion influx as an ion channel activity indicator. Finally, we assessed the biological impact of the nanodrug through cell viability and reactive oxygen species production. We showed that AMFs-induced release of one dose of capsaicin enhances TRPV1 receptors in more than 75% of hippocampal neurons, which would translate to an increased pain sensitivity. However, tonic capsaicin treatment (more than 3 doses of AMFs-induced release) desensitizes TRPV1 in more than 90% of neurons, which would result in analgesic effects. Importantly, the nanotherapy has no detrimental effects on neuronal health. The nanodrug developed here offers a promising mechanism-driven alternative for chronic pain management by enabling wireless and on-demand control of pain receptors.