Stimulation Obtained by Ultrasound for NeuroDegeneration (SOUND)

Neurodegeneration (ND) is a pathological process characterized by a progressive loss of structure and activity in neurons of specific brain areas, causing cognitive, sensory, and motor impairment until compromising even basic actions such as breathing and heart functioning.

The condition affects over 100 million people globally, and it is estimated that ND incidence will constantly increase in the next decades, because of the increasing ageing of the European population and environmental factors.

Nevertheless, the current treatments are not satisfactory, either because they become ineffective over time, e.g., pharmacological treatment, or because they are highly invasive, i.e. for deep brain stimulation or optogenetic approaches. In this landscape, nanotechnology is emerging as an innovative alternative for treating ND.

Nanomaterials offer unique features that confer them the chance to activate degenerated neurons, therefore rescuing the network activity lost in ND.

Here, we propose the preparation of a wireless, non-invasive, deep tissue penetrating nanotechnological platform for neuronal rescue upon ultrasound stimulation.

We aim to develop a hybrid nanotool based on visible light-sensitive photovoltaic polymeric nanoparticles (that proved successful in rescuing several degenerated retina models in vivo) that will be conjugated to an ultrasound sensitizer, consisting of sonoluminescent molecules capable of transducing an ultrasound signal into a fluorescent emission that can excite the polymeric nanoparticles, ultimately eliciting a neuronal response.

The construct will then be directed towards a specific neural population through a targeting moiety, consisting of an M13 bacteriophage nanoscaffold naturally possessing high targeting efficiency.

The final nanotool will be tested in different 2D and 3D in vitro models to assess its biocompatibility, brain blood barrier permeability and neural rescuing efficiency.