Lyophilization enabled disentanglement of polyethylenimine on rambutan-like silica nanoparticles for enhanced plasmid DNA delivery.

Polyethylenimine (PEI) functionalization onto nanoparticles is a widely used strategy for constructing particulate vectors for gene delivery. However, how to control the conformation of PEI chains and the resultant impact on gene transfection efficiency remains largely unexplored. Herein, we report that drying methods dramatically affect the conformation of PEI chains modified on the surface of silica nanoparticles and consequently the plasmid DNA transfection performance. Specifically, lyophilization renders less entangled PEI compared to commonly used vacuum drying as evidenced by an elevated glass transition temperature. The lyophilization induced disentangled conformation is likely associated with the solid-to-gas phase transition drying mechanism, which removes the bound crystal water content and thus reduces hydrogen bonding between amines. Moreover, we find that the stretched PEI chains on the surface of rambutan-like silica nanoparticles promote their binding capacity towards plasmid DNA molecules and thereby enhanced gene delivery and transfection efficiency. Our findings have provided new understanding about amine based polymers modified on nanoparticles, and have significant implications on the design of efficient particulate vectors for gene delivery.