HA-decorated nanoparticles as tumour-targeting nucleic acids carriers

The design of tools that allow for a targeted delivery of therapeutic cargos have a great potential in the treatment of many pathological conditions (e.g. cancer and autoimmune diseases). In the context of nucleic acids delivery, an ideal carrier should not only provide the means for their targeted delivery, it should also protect their activity by limiting their exposure to degrading agents, e.g. physical and enzymatic degradation. We here present our results in the development of nanoparticles designed to target CD44, which is overexpressed in tumours and is also the primary receptor of hyaluronic acid (HA). HA-decorated nanoparticles with a chitosan (CS) core for nucleic acid complexation were prepared. The loading efficiency and stability of siRNA were characterised, together with the nanoparticle properties (e.g. size, Z-potential). To facilitate the understanding of the intracellular trafficking of the nanoparticles, CS, HA and nucleic acid components were fluorescently labelled and 3D reconstructions of the cell-nanoparticle interaction were rendered. Endosomal escape and the consequent cytoplasmic release of the payload from the HA-decorated nanoparticles in CD44 expressing cells showed a successful and targeted delivery.