Spiropyran-based glutamate nanovalve for neuronal stimulation

Abstract

One of the main challenges in medical applications is achieving precise spatial and temporal control over the release of active molecules, such as neurotransmitters. To address this issue, we engineered a nanovalve that can deliver active molecules on demand by activating or deactivating a light-sensitive chemical barrier. This valve is composed of a polymer containing a spiropyran moiety, which can switch from a hydrophobic to a hydrophilic state upon photo-stimulation. Accordingly, the nanovalve either blocks or allows molecular diffusion through a solid-state nanopore array. Here, we demonstrate that the system blocks up to 96% of the translocation of the neurotransmitter glutamate and that the on-demand release of glutamate upon light stimulation reaches 60 μM h⁻¹, mimicking a physiological synaptic release rate. We proved its cytocompatibility and analyzed its potential for the stimulation of primary neurons and blind retinal explants by patch-clamp experiments. These results represent a milestone for the development of biomimetic neuroprostheses restoring chemical synaptic transmission lost by degeneration or delivering drugs in a light-controlled fashion.