Design and systhesis of nanoparticles for therapy and imaging of Alzheimer's disease

Various types of nanoparticles (NPs), such as Liposomes, Solid Lipid NPs and Polymeric NPs, are being extensively explored for their potentialities in the medical field. NPs are attractive tools in biomedical applications thanks to their biocompatibility, non-immunogenicity, non-toxicity, biodegradability, high physical stability, possibility of drug loading and releasing, and higher probability for surface functionalization. The project is devoted to the synthesis of NPs functionalized with amyloid-beta ligands (Aβ-ligands), imaging tools and/or blood brain barrier-transporters (BBB-transporters) for the cure and the diagnosis of Alzheimer’s disease (AD). Amyloid β (Aβ) aggregates are considered as possible targets for therapy and/or diagnosis of Alzheimer disease (AD). It has been previously shown that some small molecules targets Aβ plaques and, among them, curcumin interacts with their precursors, suggesting a potential role for the prevention or the treatment of AD. Herein, a chemoselective ligation procedure was used to generate NPs decorated with a curcumin derivative, designed to maintain all the features required for interaction with Aβ. In summary, this thesis describes the preparation and characterization of new curcumin derivatives and NPs, with affinity for Aβ peptide. They could be exploited as ligands and/or vectors for the targeted delivery of new diagnostic and therapeutic molecules for AD. The NPs preparations and the biological results were obtained in collaboration with scientists involved in a joint European project: NAD - Nanoparticles for therapy and diagnosis of Alzheimer’s Disease - 2008-2012, FP7-NMP-2007-LARGE-1-Large-scale integrating project NMP-2007-4.0-4 Substantial innovation in the European medical industry: development of nanotechnology-based systems for in-vivo diagnosis and therapy.