Wireless magnetothermal entero-modulation

Objetivo

Gastrointestinal (GI) disorders affect over 40% of the world population. Pharmacological agents that modulate cell function and subsequently impact processes involved in such disorders, suffer from limited spatiotemporal specificity and accompanying side effects. Despite the advances in the field of bioelectronic medicine which have enabled localized modulation of electrogenic cells, it still requires invasive hardware, impeding their use in soft and continuously moving organs. We recently showed that magnetic nanoparticles injected into a deep solid organ and exposed to alternating magnetic fields (AMFs), dissipate heat that can trigger localized calcium signaling mediated by endogenously expressed heat-sensitive ion channels. However, penetrating the sensitive and hollow intestine tissue is challenging. This proposal aims to develop a novel approach for remote activation of the intestine via adhesive materials. To achieve this goal, an implantable, biocompatible and stretchable magnetic gel will be designed with controlled adhesiveness, allowing for its effective adherence to tissues and detachment. The magnetic gel can be remotely controlled to dissipate heat under AMFs. Prior to attempting thermal stimulation of the intestine, a proof-of-principle demonstration will be performed in the adrenal gland, a solid organ which expresses heat-sensitive ion channels. Next, the gel properties will be tailored to the intestinal tissue and the activation of heat-sensitive ion channels in the colon will be thoroughly characterized ex vivo. Finally, in vivo entero-modulation will be demonstrated, while addressing barriers associated with use of magnetic nanomaterials in in vivo models and modulating parameters to achieve short latency between stimulation onset and cell response. Ultimately, I propose to achieve wireless ondemand control of calcium influx and neuropeptide release in the colon, to address gastric symptoms of disturbed motility and inflammatory response.