Complexation of DNA with Cationic Copolymer Micelles: Effects of DNA Length and Topology

Micelleplexes are promising gene delivery vehicles that form when DNA complexes with polycationic micelles. In this study, the influence of DNA length and topology on the structure and colloidal stability of micelleplexes was explored using a model system. The cationic micelles were composed of poly(2-(dimethylamino)ethyl methacrylate)-block-poly(n-butyl methacrylate) and were complexed with linear DNA and circular plasmids of 2442, 4708, and 7537 base pairs. The cationic micelles had a mean core radius of 8 ± 1 nm and a mean hydrodynamic radius of 34 ± 1 nm in buffer at pH 5 and 100 mM ionic strength. The formation of micelleplexes was monitored by turbidimetric titration as a function of N/P ratio (amine in micelle corona/phosphate on DNA) in acetate buffers of various ionic strengths. The structure and size evolution of micelleplexes were studied by dynamic light scattering and cryo-TEM, while the composition of micelleplexes was estimated using static light scattering. The combination of these techniq...