Inhibition of Glycation-Induced Aggregation of HumanSerum Albumin by Organic–Inorganic Hybrid Nanocomposites ofIron Oxide-Functionalized Nanocellulose

摘要

Protein aggregation leads to the transformation of proteins from their soluble form to the insoluble amyloid fibrils and these aggregates get deposited in the specific body tissues, accounting for various diseases. To prevent such an aggregation, organic–inorganic hybrid nanocomposites of iron oxide nanoparticle (NP, ∼6.5–7.0 nm)-conjugated cellulose nanocrystals (CNCs) isolated from Syzygium cumini (SC) and Pinus roxburghii (PR) were chemically synthesized. Transmission electron microscopy (TEM) images of the nanocomposites suggested that the in situ-synthesized iron oxide NPs were bound to the CNC surface in a uniform and regular fashion. The ThT fluorescence assay together with 8-anilino-1-naphthalenesulfonic acid, Congo Red, and CD studies suggested that short fiber-based SC nanocomposites showed better inhibition as well as dissociation of human serum albumin aggregates. The TEM and fluorescence microscopy studies supported similar observations. Native polyacrylamide gel electrophoresis results documented dissociation of higher protein aggregates in the presence of the developed nanocomposite. Interestingly, the dissociated proteins retained their biological function by maintaininga high amount of α-helix content. The in vitro studies withHEK-293 cells suggested that the developed nanocomposite reduces aggregation-inducedcytotoxicity by intracellular reactive oxygen species scavenging andmaintaining the Ca²⁺ ion-channel. These results indicatedthat the hybrid organic–inorganic nanocomposite, with simultaneoussites for hydrophobic and hydrophilic interactions, tends to providea larger surface area for nanocomposite–protein interactions,which ultimately disfavors the nucleation step for fibrillation forprotein aggregates.