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Different small molecules and nanomaterials have been known as inhibitors of protein misfolding and subsequent fibrillation, which marks the initiation of various degenerative conditions. This work explores the effect of polyphenol-capped gold nanoparticles on the extent of human serum albumin fibrillation. Silymarin-capped (SAuNPs), quercetin-capped (QAuNPs) and gallic acid-capped gold nanoparticles (GAuNPs) were synthesized with a uniform size range and their relative antioxidant capacity was determined through DPPH assay. The fibrillation of HSA at 65 °C was inhibited by ∼15% in the presence of SAuNPs and the process was monitored through a combination of Thioflavin T fluorescence spectroscopy, circular dichroism spectroscopy and microscopic analysis. The inhibitory effect appeared much pronounced in the case of QAuNPs (∼67%) and GAuNPs (∼60%). Using SDS PAGE analysis, we demonstrated that the different inhibitory activity of SAuNPs, QAuNPs, and GAuNPs could be attributed to the antioxidant potential of the individual nanoparticles. Our work revealed that apart from protein–nanoparticle surface interactions, the antioxidant capacity has a role in determining the effectiveness of a protein fibrillation inhibitor. Cytotoxic analysis of protein–gold nanoparticle aggregates on HaCaT cell lines further confirmed that the nanoparticles were biosafe and can be considered as active therapeutics for translational use.

Biopolymer nanoparticles functionalized with targeting ligands serve as carriers for a wide range of therapeutic payloads to desired sites of the body. Upon introduction into the blood stream, the nanoparticles tend to bind with the plasma proteins in its immediate vicinity, forming a protein corona. In this work, we have investigated the effects of differently functionalized PLGA nanoparticles on the formation of protein corona. It was observed that nanoparticles of uniform size range adsorbed protein in varying amounts and the final hard corona differed structurally with respect to nanoparticle surface functionalization. A combination of fluorescence spectroscopy and FTIR studies revealed that the association of plasma proteins with PLGA nanoparticles during corona formation was intricately guided by the nanoparticle surface chemistry. Densitometric analysis through one dimensional gel electrophoresis further showed that the plasma proteins present in the hard corona were different for each case of surface functionalization. The aggregation of plasma protein during corona formation as studied through Thioflavin T fluorescence and circular dichorism spectroscopy was also found to significantly differ with each nanoparticle type. It is evident that surface chemistry of biopolymeric nanoparticles defines the final corona form in the physiological environment, and this study on detailed understanding of nanoparticle-protein corona would help to develop nanomedicines for clinical applications.