Nanotechnology paves the way for innovative and efficient therapeutic and diagnostic agents and tools. Still, treatment of neurodegenerative disorders remains a challenging field due to therapeutic necessity to reach the brain by crossing the blood-brain barrier (BBB), one of the best gate-keeper. Multifunctional nanoparticles (NPs) offer new and improved platform to solve issues about efficacy, bioavailability and targeting ability by translocating drugs through the BBB. The ultimate goal of proposed project is development of multifunctional nano-enabled drug delivery systems for brain (BRaiND) for efficient and safe treatment of abnormalities that follow debilitating brain conditions linked to aging and degeneration. This will be achieved by following specific objectives: - design, preparation and characterization of BRaiND; - evaluation of BRaiND stability and fate in biological media; - mechanistic and quantitative assessment of interaction of BRaiND with BBB; - efficacy and safety profiling of BRaiND by a combined in vitro and in vivo approach. BRaiND will be based on selenium or gold NPs, stabilized with polyethylene gylcol and functionalized with proteins that target the brain receptors. Such multifunctionalized system will be loaded with model neuroactive agents to demonstrate its efficacy, quality and safety. Careful in vitro and in vivo testings will be performed including stability and interactions of BRaiND in different biological media, BBB permeability, and efficacy of targeting specific brain sites, neuroprotective activity, and safety profiling. SENDER work plan is based on validated and standardized methodologies, as well as emerging new experimental techniques. Considering the major challenges of translational research in neurodegenerative diseases, SENDER strategy is based on the Safe-by-Design approach and enabled by nanotechnological tools that analyze and manipulate biological processes at the nanoscale, where diseases initiate and progress.