Atomic Force Microscopy Studies of DNA Release in Gene Delivery Dynamics

This chapter reviews recent advances in the understanding of DNA release dynamics from polymeric gene delivery systems. Atomic force microscopy (AFM) has recently been applied to monitor DNA release from bioreducible polyplex nanoparticles and layer-by-layer (LbL) thin films in real time. DNA release dynamics is central to the understanding and control of gene delivery from gene delivery nano-systems. Polycations containing bioreducible disulfide bonds form interpolyelectrolyte complexes with DNA in nanoparticles and thin films. During disassembly, DNA is released in nearphysiologic conditions due to the reducing nature of the polycations. AFM is used to visualize plasmid DNA in various decondensed states from reducible polyplexes and LbL films. The studies highlight nanostructures including toroids and bundles as dominant intermediate DNA structures during DNA release.