Solute Stabilization Effects of Nanoparticles Containing Boronic Acids in the Absence of Binding Pairs

Boronic acids are widely used in materials science because of their ability to reversibly bind with diol and catechol moieties through dynamic covalent interactions in a pH- and oxidative-dependent manner. Considerably fewer studies focus on property modulation of boronic acid-based materials in the absence of a biding pair. Herein, we discuss the effects of the boronic acid-containing polymer block length on solute release kinetics from nanoparticles in a stimuli-responsive manner for on-demand delivery. In this study, ABC-type linear amphiphiles of poly(d,l-lactide) and poly(2-methacryloyloxyethyl phosphorylcholine) containing a middle block functionalized with 3-aminophenylboronic acid were synthesized by a combination of ring-opening and controlled free radical polymerizations. Nile red-loaded nanoparticles were self-assembled using a multi-inlet vortex mixer in a well-controlled manner. Release was evaluated at pH above and below the pK_a of the boronic acid and in the presence of hydrogen peroxide. Our results show that release kinetics from nanoparticles incorporating a boronic acid-functionalized interlayer were slower than those without it, and the rate could be modulated according to pH and oxidative conditions. These effects can be attributed to several factors, including the hydrophobicity of the boronic acid block as well as hydrogen bonding interactions existing between locally confined boronic acids. While boronic acids are generally utilized as boronic/boronate esters, their stabilizing effects in the absence of appropriate binding pairs are relevant and should be considered in the design of boronic acid-based technologies.