Different functionalization approaches to target micro and nano vectors toward tumor cells

Micro and nanoparticles have been recently exploited to tackle two important points in medicine namely: drug specific targeting and gene therapy. The thesis covered both aspects although concentrating a large part of my work on the first one. In detail as far as the drug specific targeting is concerned, I have used the strategy of folic acid functionalization using as micro and nano-carriers poly-vinyl alcohol microcapsules (PVA-MCs) or organically modified silica nanoparticles (ORMOSILs). PVA-MCs show high versatility, biocompatibility (Cavalieri et al, 2006) and a threedimensional water soluble network able to adsorbs different chemical compounds. In my thesis I have studied the delivery of camptothecin (CPT), a powerful and insoluble antineoplastic drug, adsorbed on PVA-MC. The microparticles have been functionalized with folic acid using two different linking procedures. In one case a chitosan-folate complex has been produced and then linked on MC surface. Chitosan has been used as spacer arm to allow a varied three-dimensional orientation of the folate group. In the other case MCs have been functionalized with lysine, that is then used to link folate. The systems, tested for localization and viability on epithelial tumor cell lines and on a healthy connective line, have been shown to display a strong preference for the tumor cells. The strategy of folate mediated active targeting has been also applied to a system of silica-based nanoemulsion (ORMOSIL). The resulting ORMOSIL-FA has been tested for the FR-mediated localization in tumor cell lines, showing that the internalization process is not totally determined by FR. As far as gene therapy is concerned I have explored the possibility to use chitosan as biocompatible carrier for plasmid DNA. Chitosan is a natural, biocompatible polymer that can interact with nucleic acids to form a transfectable nanoparticle. Aim of my work has been to clarify the suitability of some already known chitosan derivatives in macrophages transfection.