Brain-Targeted Biodegradable Nanoparticles for Innovative Fragile X Therapy

Nanomedicine is emerging effective and promising to treat several conditions. One major hurdle is the release of the drug into the brain because of the protective biological barrier, namely the blood brain barrier (BBB). Although promising findings in the recent Coronavirus outbreak have highlighted the potential of mRNA-based therapy using lipid nanoparticles as vehicles, there may be limitations, such as payload capacity and rapid clearance, leading to limited NPs circulation. Organosilica nanoparticles (OSNPs) might overcome these issues, as they are characterized by low toxicity, high drug load, and protect the activity of the enclosed drugs. Our goal is to design OSNPs that can efficiently transport molecules, such as mRNAs, within the central nervous system. We will develop low-sized OSNPs and test their safety in 2D and 3D in vitro models of the BBB, this last mimics the BBB microenvironment in vivo. The use of in vitro models is essential for optimizing experimental conditions prior to final in vivo validation, in compliance with the 3Rs principle. Subsequently, we will assess the delivery of FMR1 mRNA in vivo, evaluating key behavioral phenotypes associated with Fragile X Syndrome (FXS), as a result of BBB penetration. Our product will result beneficial for several neurological disorders via the delivering of mRNA molecules. We envision to create a safe and effective agent that can contribute to FXS therapy and other neurological conditions, representing a ground-breaking advancement in biomedicine and nanotechnology because the route of administration will be non-invasive with the strong translational potential in clinical trials.