(Closed) (NanoChemogen) Development of photoactive nanoparticles for non-invasive chemogenetic neuromodeling

The NanoChemogen projects aim to explore new nanotechnological approaches for minimally invasive deliver of neuromodulators to the brain with high spatiotemporal resolution. To address this challenge, we will explore the potential of focused ultrasound (FUS), an emergent technology that, comparatively with visible light, affords much deeper penetration in biological tissues, to trigger the delivery of drugs into the brain region of interest. Our strategy consists of the use of biocompatible mechanoluminescent nanoparticles, that emit visible light upon excitation by FUS, acting as transducers that convert ultrasound into light and trigger the release of selected drugs encapsulated in photoresponsive mesoporous silica nanoparticles.

To examine the in vitro and in vivo feasibility of this approach, we will explore the spatiotemporal activation of designer receptors exclusively activated by designer drugs (DREADDs) in specific neurons. For that, the designer ligand clozapine-N-oxide (CNO) will be encapsulated inside mesoporous silica nanoparticles functionalized with photoresponsive nanovalves. Then, the ability of these nanomaterials to release the drug, upon stimulation with FUS in the presence of mechanoluminescent nanoparticles and modulate neural activity will be investigated.