Physicochemical stability and protein corona profiling on the interaction of iron oxide nanoparticles with human tears.

The integration of nanotechnology into ophthalmology represents a promising frontier for the development of precision diagnostics and therapeutics aimed at enhancing ocular health. While the systemic interactions of iron oxide nanoparticles (IONPs) with blood plasma have been extensively studied, their biomolecular interactions within the ocular environment, particularly human tears, remain largely unexplored. In this study, we comprehensively investigate the physicochemical behaviour and proteomic corona interactions of IONPs upon exposure to human tear extracts. Dynamic light scattering (DLS) revealed a modest increase in hydrodynamic diameter from ∼115 ± 3.3 nm to ∼139 ± 0.7 nm, accompanied by a reduction in the zeta potential (ZP) from ∼-36 ± 1.7 mV to ∼-29 ± 1 mV, likely due to protein adsorption. Proteomic profiling via liquid chromatography-mass spectrometry (LC-MS/MS) identified that 25 tear proteins got adsorbed onto the IONPs when compared to tear alone samples with 91 proteins, revealing the association of Lysozyme C, Lactotransferrin, Mammaglobin B, Lipocalin-1, keratins, immunoglobulins, opiorphin propeptide, Keratin II, Protein S100 and mesothelin proteins implicated in bacteriolysis, iron transport, transcriptional regulation, immune response, the cytoskeleton, tissue integrity, nucleotide binding, inflammation regulation, skin tissue formation, endogenous inhibition, microbiome homeostasis and signal transduction. These findings provide protein dynamics of the ocular nano-bio interface, emphasizing the influence of tear protein composition on IONPs. Our results highlight how tear protein corona formation defines the physicochemical stability of IONPs within the human tear environment and provide a basic understanding of these alterations, which may influence IONP-based ocular therapeutic systems.