Remote neurostimulation through an endogenous ion channel using a near infrared light-activatable nanoagonist

The development of noninvasive approaches to precisely control neural activity in mammals is highly desirable. Here we utilized the ion channel TRPA1 as a proof of principle, demonstrating remote near-infrared (NIR) activation of endogenous channels in the neural structures of living mice through an engineered nanoagonist. This achievement enables specific neurostimulation in wild-type, non-genetically modified mice. Initially, target-based screening identified flavins as photopharmacological agonists, allowing for the photoactivation of TRPA1 in sensory neurons upon UVA/blue light illumination. Subsequently, upconversion nanoparticles (UCNPs) were customized with an emission spectrum aligned to flavin absorption and conjugated with flavin adenine dinucleotide, creating a nanoagonist capable of NIR activation of TRPA1. Following the intrathecal injection of the nanoagonist, noninvasive NIR stimulation allows precise bidirectional control of nociception in mice through the remote activat..., , , Remote neurostimulation through an endogenous ion channel using a near infrared light-activatable nanoagonist

[https://doi.org/10.5061/dryad.mgqnk996r](https://doi.org/10.5061/dryad.mgqnk996r)

Our manuscript demonstrates the specific and noninvasive stimulation of neural activity in mice using a NIR-activated agonist for an endogenous ion channel, resulting in the remote control of pain.

The files are available in OriginPro or GraphPad Prism formats and are organized by figure panels corresponding to those in the original manuscript. Each file contains raw data used to produce the figure panels. An exception is made for Figure 4 panels, where the raw data sets are organized in Excel spreadsheets or text files, and the graphs generated from the raw data are provided in PDF format. Each file includes a legend describing the original experiment.

Fig. 1A shows the whole-cell currents recorded at +80 and -80 mV in a human TRPA1-expressing HEK 293 cell in response to sequential applicatio...