Polymeric and bio-hybrid nanovectors for drug delivery and imaging devices.

Nanotechnology applied to the Medicine is providing new tools to the current therapeutic and diagnostic approaches to fight cancer and other diseases. However, many of the proposed nanodevices show some deficits related to both their inherent properties and performance, and the synthetic strategies proposed for their production. In the present work, a new promising approach based on e-beam radiation-induced radical crosslinking of a water soluble, biocompatible synthetic polymer has been developed. In particular, the possibility of generating Poly-N-(Vinyl- Pyrrolidone)(PVP)-based nanocarriers, i.e. nanogels with a base PVP structure, tailored physico-chemical properties (particles size distribution, surface charge density) and multifunctionality has been explored. A thorough product analysis on the generated nanoparticles through different characterization techniques, such as dynamic and static light scattering, photo-correlation spectroscopy, FT-IR, Raman, solid state NMR and XPS spectroscopies, SEM and AFM, has been carried. PVPbased nanogels have been then used as building blocks for the assembly of tumortarget “composite” nanodevices. “Model” ligands with various biological functions and drugs have been conjugated to the nanogels. Moreover, the biocompatibility and localization pattern of the nanocarriers in cell cultures have been evaluated. It has been demonstrated that all the NGs produced are biocompatible and able to be internalized by cells. Furthermore, the many functional groups grafted on the NGs are available for coupling reactions with bioactive molecules, such as targeting moieties, drugs and metal-ions chelating agents. This collective evidence validates the generated nanostructures for the intent they have been designed for, i.e. as nanocarriers in the biomedical field. E-beam irradiation using industrial type accelerators has demonstrated to be a viable manufacturing process since it grants high yields in terms of recovered product and high throughputs. Moreover, through a proper selection of the experimental parameters, this approach has allowed to obtain NGs with the desired properties, in terms of size, surface charge density, degree of crosslinking and functionality. All the evidences collected in this study, in terms of favorable properties-byprocess of the nanostructures generated and inherent advantages in the manufacturing process developed, can represent the fundaments for a further development and evaluation of this versatile “nanomaterial platform” for the treatment and diagnosis of various diseases, and cancer in particular.