Electrostatic Interactions between Acid-/Base-Containing Polymer Nanoparticles and Proteins: Impact of Polymerization pH

Electrostatic interaction between synthetic polymer nanoparticles (NPs) and proteins is of considerable importance in the design of NPs that capture, neutralize, and deliver target molecules in a biological milieu. Ionizable functional groups, such as carboxylic acids and amines, are often introduced to NPs to tune the affinity with target bio-macromolecules through electrostatic attraction and repulsion. However, acids/bases are not always ionized at a physiological pH because acidities of the functional groups depend on the microenvironment around the acids/bases that are imprinted during the polymerization process. Here, we show that electrostatic interaction between acid-/base-containing NPs and target proteins strongly depends on the pH of the solution during the NP polymerization process. To prepare NPs that capture target proteins by electrostatic interactions at physiological pH, NPs must be polymerized within a pH range where the acid/base monomer is ionized. Acid-/base-containing NPs that exhibit completely different interactions with the proteins can be prepared by changing the polymerization pH without changing monomer compositions. Our results indicate that polymerization pH should be carefully tuned to design acid-/base-containing NPs that show desired affinity to all proteins in a biological milieu and to proteins of interest.