Surface Functionalization of Nanoparticles for Enhanced Electrostatic Adsorption of Biomolecules

Electrostatic adsorption plays a crucial role in nanoparticle-based drug delivery, enabling the targeted and reversible loading of biomolecules onto nanoparticles. This review explores the fundamental mechanisms governing nanoparticle-biomolecule interactions, with a focus on electrostatics, van der Waals forces, hydrogen bonding, and protein corona formation. Various functionalization strategies-including covalent modification, polymer coatings, and layer-by-layer assembly-have been employed to enhance electrostatic binding; however, each presents trade-offs in terms of stability, complexity, and specificity. Emerging irradiation-based techniques offer potential for direct modulation of surface charge without the addition of chemical groups, yet they remain underexplored. Accurate characterization of biomolecule adsorption is equally critical; however, the limitations of individual techniques also pose challenges to this endeavor. Spectroscopic, microscopic, and electrokinetic methods each contribute unique insights but require integration for a comprehensive understanding. Overall, a multimodal approach to both functionalization and characterization is essential for advancing nanoparticle systems toward clinical drug delivery applications.