Multifunctional nanoparticles for cancer therapy

In the last few years, great interest in the pharmaceutical nanotechnology field has been devoted to the development of multifunctional nanoparticles for cancer therapy, in order to improve drug efficacy and selectivity as well as to revert multidrug resistance. In this context, the general aim of this thesis was to combine different treatment modalities by the co-delivery of conventional chemotherapeutics and a bioactive species with complimentary activity. To this purpose, double-coated biodegradable nanoparticles (dcNPs) targeted to cancer cells overexpressing CD44 receptor were developed. The core of dcNPs was made of poly(lactic-co-glycolic acid) and entrapped preferentially hydrophobic drugs. Then a first polycationic layer made of polyethyleneimine (PEI), able to embed hydrophilic anionic drugs, and a second polyanionic layer of low molecular weight hyaluronic acid (HA) were deposited on the nanocore. We explain how to build NPs through a layer-by-layer strategy and how to entrap a chemotherapeutic in the core together with a photosensitizer or a plasmid adsorbed in the shell. Double-coated NPs demonstrated specificity toward different cancer cell lines, which resulted in increased cytotoxicity of the delivered chemotherapeutic as compared to its free counterpart. It is demonstrated that dcNPs loaded also with a photosensitizer or a plasmid to rpL3 potentiate the cytotoxicity of the chemotherapeutic alone. In conclusion, dcNPs turn out to be a versatile platform to deliver drug combinations in target cancer cells and can be considered for further testing in mice models of tumor