title: Ion-Mobility-Based Quantification of Surface-Coating-Dependent Binding of Serum Albumin to Superparamagnetic Iron Oxide Nanoparticles.
abstract: Protein binding and protein-induced nanoparticle aggregation are known to occur for a variety of nanomaterials, with the extent of binding and aggregation highly dependent on nanoparticle surface properties. However, often lacking are techniques that enable quantification of the extent of protein binding and aggregation, particularly for nanoparticles with polydisperse size distributions. In this study, we adapt ion mobility spectrometry (IMS) to examine the binding of bovine serum albumin to commercially available anionic-surfactant-coated superparamagnetic iron oxide nanoparticles (SPIONs), which are initially ∼21 nm in mean mobility diameter and have a polydisperse size distribution function (geometric standard deviation near 1.4). IMS, carried out with a hydrosol-to-aerosol converting nebulizer, a differential mobility analyzer, and a condensation particle counter, enables measurements of SPION size distribution functions for varying BSA/SPION number concentration ratios. IMS measurements suggest that initially (at BSA concentrations below 50 nM) BSA binds reversibly to SPION surfaces with a binding site density in the 0.05-0.08 nm(-2) range. However, at higher BSA concentrations, BSA induces SPION-SPION aggregation, evidenced by larger shifts in SPION size distribution functions (mean diameters beyond 40 nm for BSA concentrations near 100 nM) and geometric standard deviations (near 1.3) consistent with self-preserving aggregation theories. The onset of BSA aggregation is correlated with a modest but statistically significant decrease in the specific absorption rate (SAR) of SPIONs placed within an alternating magnetic field. The coating of SPIONs with mesoporous silica (MS-SPIONs) as well as PEGylation (MS-SPIONs-PEG) is found to completely mitigate BSA binding and BSA-induced aggregation; IMS-inferred size distribution functions are insensitive to BSA concentration for MS-SPIONs and MS-SPIONs-PEG. The SARs of MS-SPIONs are additionally insensitive to BSA concentration, confirming the SAR decrease is linked to BSA-induced aggregation.
authors: Seongho
authors: S
authors: Jeon
authors: Kanomax-FMT , White Bear Lake, Minnesota 55110, United States.
authors: Derek R
authors: DR
authors: Oberreit
authors: CT Associates , Eden Prairie, Minnesota 55344, United States.
authors: Gary
authors: G
authors: Van Schooneveld
authors: Zhe
authors: Z
authors: Gao
authors: John C
authors: JC
authors: Bischof
authors: Christy L
authors: CL
authors: Haynes
authors: Christopher J
authors: CJ
authors: Hogan
mesh_terms: D000818:Animals; D058185:Magnetite Nanoparticles; D012710:Serum Albumin, Bovine; D012822:Silicon Dioxide; D013499:Surface Properties
chemical_list: D058185:Magnetite Nanoparticles; D012710:Serum Albumin, Bovine; D012822:Silicon Dioxide
keywords: hyperthermia; ion mobility spectrometry; mesoporous silica; protein-induced aggregation; protein−nanoparticle conjugates; superparamagnetic nanoparticles