Monodisperse Boronate Polymeric Particles Synthesized by a Precipitation Polymerization Strategy: Particle Formation and Glycoprotein Response from the Standpoint of the Flory–Huggins Model

The development of a highly specific recognition system for glycoprotein capture from complex biological samples is a prerequisite to the success of mass spectra-based glycoproteomics analysis. To achieve this purpose, a one-pot precipitation polymerization (PP) strategy with a novel solvent system composed of water/ethanol (4:1, v/v) is described for preparing boronate-affinity polymeric micro/nano particles using 4-vinylphenylboronic acid (VPBA) as the functional monomer and N,N'-methylenebis(acrylamide) (MBA) alone or together with divinylbenzene (DVB) as the cross-linker(s). The proposed polymerization strategy not only affords monodisperse polymeric submicrometer particles with a smooth surface and controllable size, ranging from 300 to 700 nm, but also increases the loading capacity of boronic acid, which could hardly be achieved by other polymerization methods, thus leading to the specific recognition of glycoproteins. The effects of solvent systems and monomers on the morphology and boronate-affinity capacity of prepared materials were further investigated based on the Flory-Huggins model. It was proved that the reaction rate of various monomers during particle formation might be the key factor affecting the affinity capacity for glycoproteins. Our results demonstrated that under the theoretical guidance of the Flory-Huggins model the PP strategy with a selected monomer and solvent system might provide a good approach to prepare submicrometer polymer particles with plenty of boronic acid groups on the surface to achieve a highly selective enrichment of glycoproteins.