Synthesis and self-assembly of polyzwitterionic phenylboronic acid-containing double hydrophilic block copolymers

Abstract

Abstract Double hydrophilic block copolymers self-assemble into smart materials with promising applications in nanomedicine. However, such practical applications require thoroughly understanding the underlying mechanisms of this self-assembly process and the effects of external stimuli on the resulting materials. Thus, we report the post-polymerization modification of a pH-responsive double hydrophilic diblock copolymer (poly(ethylene oxide)-b-poly(4-vinyl pyridine)) by stimuli-responsive, diol-binding 2-bromomethyl-4-fluorophenylboronic acid and the comprehensive study of the self-assembly properties of this polyzwitterionic polymer for potential applications in the delivery of functional diols, including pharmaceutical drugs, steroids and sugars. For this purpose, we performed simple, robust and reproducible quaternization reactions at three different degrees (25, 50 and 100%) by varying the composition of the initial mixture and confirmed full control over the degree of quaternization by proton nuclear magnetic and infrared spectroscopy. Our results showed that the degree of quaternisation strongly affects the solubility of these polymers in basic solutions because PBA adopts a tetragonal conformation with a negative charge on boron at pH values higher than the pKA of PBA. Nevertheless, the specific PBA (anionic vs neutral) form of these polymers can be differentiated by 11B NMR, regardless of the degree of quaternization. In turn, the pH of the solvent affected the intensity of the NMR signals, thus suggesting the formation of kinetically frozen nanoparticles, in line with the results from both static and dynamic and light scattering, with no indication of particle dissociation at low concentrations. Moreover, electrophoretic light scattering showed linear, albeit opposite (direct and inverse) correlations between the degree of quaternization and the zeta potential in water and 0.1M HCl, respectively. When adsorbed to a mica surface, these nanoparticles predominantly displayed globular shapes under atomic force microscopy. Therefore, our high-throughput and low-cost nanofabrication method combining the stimuli-responsive behaviour of a double hydrophilic block copolymer with the unique chemical properties of pH-responsive diol-binding phenylboronic acid functional groups establishes an experimental paradigm for the preparation of nanocarriers for biomedical applications, such as targeted drug delivery.