Inhibition of Glycation-Induced Aggregation of Human Serum Albumin by Organic–Inorganic Hybrid Nanocomposites of Iron Oxide-Functionalized Nanocellulose

Abstract

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 maintaining a high amount of α-helix content. The in vitro studies with HEK-293 cells suggested that the developed nanocomposite reduces aggregation-induced cytotoxicity by intracellular reactive oxygen species scavenging and maintaining the Ca2+ ion-channel. These results indicated that the hybrid organic–inorganic nanocomposite, with simultaneous sites for hydrophobic and hydrophilic interactions, tends to provide a larger surface area for nanocomposite–protein interactions, which ultimately disfavors the nucleation step for fibrillation for protein aggregates.

Multifunctional Gold Nanoparticle-Conjugated Cellulose Nanoonions Alleviate Aβ42 Fibrillation-Induced Toxicity via Regulation of Oxidative Stress and Ion Homeostasis

“…It should be mentioned here that DH− CNO and LC−CNO also showed inhibition toward HEWL and Aβ42 aggregation, which is in contrast to our previous report where plant-based CNCs were found to initially enhance the aggregation process. 52 Thus, it can be suggested that changing the morphology from CNC to CNO provided the appropriate curvature for interaction which possibly helped in the inhibition of protein aggregates.…”

Nanocellulose, a versatile platform: From the delivery of active molecules to tissue engineering applications

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Fig. 6 (a) Reaction of CDAP treatment on BNC for protein conjugation [ 80 , 189 ]; (b) Comparison of BSA uptake (left) and release (right) profiles through conventional loading and high-speed loading technique [ 186 ]; (c) in vitro protein release profile from nanocellulose hydrogels within first 48 h [ 190 ]; (d) Schematic presentation of inhibition of glycation-induced aggregation of HSA by Iron Oxide-Functionalized nanocellulose [ 191 ].

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“…In another study, Singla et al. fabricated an organic-inorganic nanocomposite of CNCs conjugated with iron oxide nanoparticles to inhibit HSA protein aggregation [ 191 ]. In vitro studies have shown that CNC nanocomposites reduce aggregation-induced cytotoxicity in HEK-293 cells by maintaining Ca 2+ ion channels and scavenging intracellular oxygen molecules ( Fig.…”

“…Thus, the results presented that nanocomposite provides a larger surface area for nanocomposite-protein interactions by opening simultaneous sites for hydrophilic and hydrophobic interactions. Even though the nanocomposite exhibits promising results, more research is required to declare this nanocomposite as a drug delivery mediator [ 191 ]. Nanocellulose-based protein delivery is shown in Table 5 .…”

“… Injection, compression [ 193 ] BNC-methoxylated pectin HSA Controlled release of molecules. [ 194 ] NC Chlorotoxin Brønsted acid ionic liquids used as both solvent and catalyst Dispersion [ 188 ] CNF–Ca 2+ /Mg 2+ RGD peptides Promising hydrogels for 3D cell culture systems [ 195 ] Ca 2+ -CNF hydrogel BSA, lysozyme, fibrinogen Large size and positive charge proteins show sustained release; Positive charge protein increased strength of hydrogel, Sustained protein activity Simple soaking method [ 190 ] BNC- g -Poly(acrylic acid) hydrogels BSA Excellent compatibility and safe for oral protein delivery Irradiation [ 196 ] CNC-ED-iron oxide HSA Disfavors inhibition of protein aggregation Dispersion, Sonication [ 191 ] RGD; arginylglycylaspartic acid, HSA; Human Serum Albumin, BSA; Bovine Serum Albumin. …”