Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic – Neutral Hydrophilic Block Polymers
2018-12-13T16:56:05Z (GMT) by
Polyelectrolyte complex micelles (PCMs, core-shell nanoparticles formed by complexation of a polyelectrolyte with a polyelectrolyte-hydrophilic neutral block polymer) offer an attractive solution to the critical problem of delivering therapeutic nucleic acids, but few structure-property studies have been carried out to date. We present data comparing oligonucleotide PCMs formed with poly(vinylbenzyl trimethylammonium) as the cationic block to those using poly(lysine), which is more commonly used. Despite its higher charge density, increased hydrophobicity, and permanent charge, pVBTMA appears to complex DNA more weakly than does poly(lysine). Using small angle X-ray scattering and electron microscopy, we find that, at physiological ionic strength, PCMs formed from both cationic blocks exhibit very similar structure-property relationships, with PCM radius determined by the cationic block size and shape controlled by the hybridization state of the oligonucleotides. These observations narrow the design space for optimizing therapeutic PCMs and provide new insights into the rich polymer physics of polyelectrolyte self-assembly.