The role of hydrophobicity in cell penetration and gene delivery by cationic copolymers

Non-viral gene delivery provides potential for a broad range of biomedical innovations, from vaccines to agriculture. However, there remains a need for efficient, non-toxic delivery agents that can enter cells and deliver genetic material. We have developed positively charged block copolymers that are able bind nucleic acids, forming so-called polyplexes. Through modification of the polymer hydrophobicity, we have been able to tune the cell-penetrating behaviour of these polymers and enhance their ability to reversibly bind RNA to function as effective gene delivery vectors. Here, we propose to use neutron reflectometry to structurally investigate the role of hydrophobicity on the interaction of these compounds with models of the eukaryotic cell membrane, and their ability to deposit genetic material. This will further the design of next-generation non-viral gene delivery vectors.