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

Abstract

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.

Nano-Proteolysis Targeting Chimeras (Nano-PROTACs) in Cancer Therapy

“…AS NDDS possess large cores with a specific surface area, they can interact with various drugs to deliver multiple drugs and realize combination therapy. Furthermore, some nanocarriers have intrinsic functions, such as photothermal conversion, 115 reactive oxygen-generating ability, 116 and neutralizing acid microenvironments, 117 , 118 thus, achieving synergistic effects.…”

Polymer Nanoparticles with Uniform Monomer Sequences for Sequence‐Specific Peptide Recognition

“…It should be noticed that arrangement of the oligomers in NPs is not controlled, and thus the cooperative binding sites for the target are not uniform in this study. The NPs with well controlled arrangement of oligomers would be achieved in the future by using molecular imprinting [8][9][10][11][12][13][14] and/or affinity purification [14][15][16][17] techniques. The use of polymer/molecular support with uniform structure such as uniform polymers [54,55] dendrimers, [51,56,57] precision oligomers [34,40,43,48] and biomacromolecules including peptides, [59] nucleic acids [35,58] and proteins [41,42] and would enable full control of the arrangement of oligomers.…”

“…[1,2] NPs that capture a given target can be prepared by the radical copolymerization of functional monomers that interact with the target molecules. [3][4][5][6][7] Molecular imprinting [8][9][10][11][12][13] and/or affinity purification [14][15][16][17] techniques enable the creation of binding site with strong affinity for the target molecules. It has also been reported that NPs can recognize and neutralize target molecules in the bloodstream of living animals.…”

Green Hydrogel Synthesis: Emphasis on Proteomics and Polymer Particle-Protein Interaction

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