Surface Potential Modulation in Boronate-Functionalized Magnetic Nanoparticles Reveals Binding Interactions: Toward Magnetophoretic Capture/Quantitation of Sugars from Extracellular Matrix

Abstract

Phenylboronic acids (BAs) are important synthetic receptors that bind reversibly to cis-diols enabling their use in molecular sensing. When conjugated to magnetic iron oxide nanoparticles, BAs have potential for application in separations and enrichment. Realizing this will require a new understanding of their inherent binding modes and measurement of their binding capacity and their stability in/extractability from complex environments. In this work, 3-aminophenylboronic acid was functionalized to superparamagnetic iron oxide nanoparticles (MNPs, core diameter 8.9 nm) to provide stable aqueous suspensions of functionalized particles (BA-MNPs). The progress of sugar binding and its impact on BA-MNP colloidal stability were monitored through the pH-dependence of hydrodynamic size and zeta potential during incubation with a range of saccharides. This provided the first direct observation of boronate ionization pK a in grafted BA, which in the absence of sugar shifted to a slightly more basic pH than free BA. On exposure to sugar solutions under MNP-limiting conditions, pK a moved progressively to lower pH as maximum capacity was gradually attained. The pK a shift is shown to be greater for sugars with greater BA binding affinity, and on-particle sugar exchange effects were inferred. Colloidal dispersion of BA-MNPs after binding was shown for all sugars at all pHs studied, which enabled facile magnetic extraction of glucose from agarose and cultured extracellular matrix expanded in serum-free media. Bound glucose, quantified following magnetophoretic capture, was found to be proportional to the solution glucose content under glucose-limiting conditions expected for the application. The implications for the development of MNP-immobilized ligands for selective magnetic biomarker capture and quantitation from the extracellular environment are discussed.