PROBING PROTEIN CORONA AND NANOPARTICLE AGGREGATION IN BIOLOGICAL MEDIA VIA X-RAY PHOTON CORRELATION SPECTROSCOPY

In biological systems, nanoparticles interact with biomolecules, leading to the formation of a protein corona that can trigger uncontrolled aggregation.^1,2 Understanding how nanoparticles behave in biological fluids is critical for advancements in nanomedicine. Conventional colloid characterization techniques, often limited to diluted suspensions in simple media, fail to probe the interactions occurring in complex biological environments.³ In this study,⁴ we present a successful demonstration of X-ray photon correlation spectroscopy (XPCS) in monitoring the dynamics of silica nanoparticles, highlighting its efficacy in capturing changes induced by exposure to complex biological environments. The diffusion coefficients were determined using a single exponential model, showing all silica nanoparticles exhibited Brownian motion, regardless of diameter, media complexity, or PEG functionalization. The Stokes-Einstein equation provided hydrodynamic diameters for all nanoparticle sizes. XPCS identified in situ variations in bare silica nanoparticle diffusion due to protein corona formation and aggregation while confirming no interaction between proteins and PEGylated nanoparticles. Notably, all experiments were conducted in highly concentrated, complex media without dilution or alteration, a feat not achievable by other techniques.

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