Stimulation Obtained by Ultrasound for NeuroDegeneration (SOUND)

Project Information

SOUND

Grant agreement ID: 101108198

DOI

10.3030/101108198

Project closed

EC signature date 19 April 2023

Start date 1 October 2023

End date 30 June 2026

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 174 928,08

Coordinated by

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Italy

Periodic Reporting for period 1 - SOUND (Stimulation Obtained by Ultrasound for NeuroDegeneration (SOUND))

Reporting period: 2023-10-01 to 2026-06-30

Summary of the context and overall objectives of the project

Neurodegenerative disorders, including Alzheimer's and Parkinson's disease, represent one of the greatest healthcare challenges facing Europe due to an ageing population and the limited availability of effective therapies. One of the major obstacles to the treatment of central nervous system diseases is the blood-brain barrier (BBB), a highly selective biological interface that prevents most therapeutic agents from reaching the brain. Developing safe and efficient strategies for targeted brain delivery is therefore a key scientific priority with the potential to improve future treatments for neurological disorders.

The SOUND project aimed to address this challenge by developing an innovative biomimetic nanotechnology platform combining semiconducting polymer nanoparticles with filamentous M13 bacteriophages as biological delivery vectors. The long-term vision was to create a modular system capable of crossing the BBB, selectively targeting neuronal cells and, ultimately, enabling minimally invasive ultrasound-mediated neuronal stimulation. By integrating expertise from nanotechnology, biotechnology and neuroscience, the project sought to establish the fundamental technological building blocks required for future therapeutic applications.

During the project, the research strategy evolved to independently develop and validate the individual components of the platform before their final integration. This modular approach reduced the technological risks associated with such a complex multidisciplinary system while generating new knowledge in nanoparticle engineering, biomimetic brain delivery and advanced in vitro BBB models.

The project contributes to European priorities in health research by advancing innovative technologies for brain-targeted drug delivery, promoting interdisciplinary research and strengthening the development of next-generation nanomedicine platforms. Beyond its scientific outcomes, the fellowship also fostered knowledge exchange across complementary disciplines, contributing to the development of new expertise at the interface between materials science, biotechnology and neuroscience.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The SOUND project followed a multidisciplinary approach combining nanotechnology, biotechnology and neuroscience to develop the technological components required for a biomimetic platform for targeted brain delivery. During the project, the research strategy evolved towards the independent development and validation of each component of the system, enabling substantial scientific progress despite the technical challenges associated with the complete integration of the platform.

A major achievement was the establishment of M13 bacteriophages as biomimetic vectors for brain delivery. Comprehensive protocols for bacteriophage production, purification and quality control were developed, together with advanced biological validation workflows. The interaction of bacteriophages with cells was systematically investigated, demonstrating excellent biocompatibility, efficient cellular uptake and intracellular trafficking. Furthermore, bacteriophages successfully crossed both 2D and 3D in vitro blood-brain barrier models while preserving their structural integrity and biological functionality, highlighting their potential as delivery vectors for central nervous system applications.

Significant advances were also achieved in the development of the nanomaterial component of the platform. A reproducible synthesis protocol for monodisperse P3HT nanoparticles below 100 nm was established, overcoming an important technological limitation. In addition, a new bioorthogonal functionalisation strategy based on clickable azide-functionalised P3HT nanoparticles was developed, enabling efficient antibody conjugation while preserving nanoparticle stability and biological activity. These results provide a versatile platform for the future functionalisation of semiconducting nanoparticles with targeting biomolecules.

To better understand bio–nano interactions, bacteriophage assembly with gold nanoparticles was investigated as a model system. The study demonstrated the spontaneous formation of stable hybrid nanostructures while preserving bacteriophage morphology, infectivity and biological functionality, providing valuable insights into the future integration of biological vectors with functional nanomaterials.

The project also established advanced experimental workflows for evaluating neuronal compatibility. Primary neuronal cultures and electrophysiological protocols were successfully implemented, demonstrating that bacteriophages do not alter intrinsic neuronal membrane properties or neuronal excitability. This finding supports their use as safe biological targeting vectors for future neuromodulation applications.

Overall, although the complete ultrasound-responsive Ph-US-P3HT platform could not be assembled within the duration of the fellowship, the project successfully established its key technological and biological building blocks. The work generated two peer-reviewed scientific publications, several proof-of-concept results and robust experimental methodologies that significantly reduce the technological risks associated with the future development of multifunctional biomimetic platforms for targeted brain delivery.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The SOUND project established several of the key technological and biological building blocks required for the future development of biomimetic brain-targeting platforms. The project demonstrated that M13 bacteriophages can serve as efficient biological delivery vectors, capable of crossing in vitro blood-brain barrier models while preserving structural integrity, biological functionality and neuronal targeting capability. In parallel, robust methodologies were developed for the preparation of monodisperse and biofunctionalisable P3HT nanoparticles, together with reproducible workflows for nanoparticle conjugation, bacteriophage production and purification, advanced blood-brain barrier models and neuronal functional evaluation.

These results significantly reduce the technological risks associated with the future implementation of multifunctional bio–nano delivery systems and provide versatile experimental platforms that can be applied beyond the original scope of the project, including targeted drug delivery, nanomedicine and biomimetic therapeutic technologies.

Further uptake of the project results will require the integration of the validated biological and nanotechnological components into a single multifunctional platform, followed by in vivo validation of brain delivery and therapeutic efficacy. The methodologies, protocols and proof-of-concept results generated during the fellowship provide a strong foundation for future collaborative research, technology development and potential translational applications. The project therefore contributes to advancing innovative strategies for targeted treatment of neurological disorders while strengthening European expertise in interdisciplinary nanomedicine and biotechnology.