NMR studies of PEG chain dynamics on mesoporous silica nanoparticles for minimizing non-specific binding

Mesoporous silica nanoparticles (MSNs) have garnered significant attention for diverse bioscience applications due to their tunable surface properties and high biocompatibility. Functionalization with hydrophilic polymers like poly(ethylene glycol) (PEG) via silane chemistry is commonly employed to reduce non-specific protein adsorption and enhance stability in physiological environments. However, characterizing surface ligands, particularly in aqueous environments, remains a key challenge. In this study, we utilized a comprehensive suite of nuclear magnetic resonance (NMR) techniques, including ¹H quantitative NMR (qNMR), diffusion-ordered spectroscopy (DOSY), and relaxation time measurements (T₁ and T₂), to investigate PEG chain dynamics and conformation on MSN surfaces. Our analysis revealed the relationship between PEG grafting density and chain mobility, demonstrating a transition to a dense brush conformation at higher densities. DOSY and T₂ experiments enabled the differentiation of covalently bound PEG from loosely adsorbed molecules. This approach provided a robust method for evaluating the efficacy of surface functionalization, ensuring the quality and consistency of PEGylated nanoparticles. Furthermore, we examined the relationship between NMR-derived parameters and protein adsorption resistance, demonstrating that densely packed PEG chains with a "dense brush" conformation can effectively reduce non-specific adsorption of human serum albumin. These findings provided valuable insights into the design of PEGylated MSNs, supporting improved quality, consistency, and functionality for biomedical applications.