Plasmid‐Templated Shape Control of Condensed DNA–Block Copolymer Nanoparticles

Plasmid condensation by cationic polymers in aqueous solutions has been widely used to prepare DNA nanoparticles with diameters ranging from tens to hundreds of nanometers.[1] Although many of these polycation–DNA nanoparticles display relatively high levels of transfection efficiency in cell culture, their performance in vivo has been disappointing.[2] This low in vivo delivery efficiency partly results from insufficient control over the physical properties and colloidal stability of the nanoparticles. Several methods have been developed to improve colloidal stability of DNA nanoparticles in physiological media, including polyethylene glycol (PEG)-conjugation, polyionic coating, and condensing DNA into polyelectrolyte micelles.[3] However, until now there has been no effective method to control and tune the shape of plasmid DNA-containing nanoparticles within this size range. This limitation is particularly pressing in view of several recent studies that show the importance of nanoparticle shape in regulating their cellular uptake and in vivo transport,[4–6] as demonstrated for the uptake of gold nanoparticles by macrophages,[7] for margination dynamics of nanoparticles in blood vessels,[6] and for the tissue distribution and circulation stability and thus drug delivery efficiency of organic and inorganic nanoparticles.[5,8] We note that none of these shaped nanoparticles have been used to package and deliver plasmid DNA.