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

Abstract

Inhibition of hen egg white lysozyme (HEWL) and Aβ42 fibrillation have been established as the main models for the treatment of systemic lysozyme amyloidosis and Alzheimer’s disease (AD), respectively. Several antiamyloidogenic nanomaterials have been developed over the period; however, their intracellular mechanism of action is still not well understood. In this context, plant-based, gold-conjugated, injectable, hydrophilic cellulose nanoonions (CNOs), viz., DH–CNO (∼60 ± 5 nm) and LC–CNO (∼55 ± 12 nm), were developed from their respective hydrophobic cellulose nanocrystals (DH–CNC and LC–CNC) using a single-step chemical template-mediated process. This unique nanocellulose architecture was chemically and morphologically characterized by various spectroscopic and microscopic techniques. Further, the different biophysical studies documented marked the inhibition/disintegration potential of gold-conjugated LC–CNO against HEWL and Aβ42 peptide aggregation. It was further observed that inhibition of protein fibrillation could be achieved within ∼10 min when the same materials were used under photoirradiation conditions. In vitro protein aggregation studies using HEK293 cells suggested that gold-conjugated LC–CNO could effectively reduce the cellular toxicity via regulation of oxidative stress and ion homeostasis. The outcome of the present study will help in designing cellulose-based novel functional nanochaperones against various neurodegenerative diseases.

Agarose/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators

“…This could also be due to changes in oxygen levels leading to oxidative stress which can influence mitochondrial function. There are very few studies that have examined the effect of nanocellulose on oxidative stress, but some in vivo research has suggested that various forms of nanocellulose and cellulose nanocrystal-derived nano-onions can induce a slight increase in reactive oxygen species (ROS) generation in gut epithelium ( DeLoid et al, 2019 ), and modulate oxidative stress in HEK293 cells ( Abidi et al, 2021 ). Cationic derivatives of crystalline crystalline nanocellulose have induced mitochondrial ROS and ATP release in a mouse macrophage cell line (J774A1) and peripheral blood mononuclear cells ( Sunasee et al, 2015 ).…”

Erythrocyte Membrane Cloaked Cytokine Functionalized Gold Nanoparticles Create Localized Controlled Inflammation for Rapid In Vitro Wound Healing

“…For precise characterization of the attachment of TNF-α and IL-6 on the AuNPs, MALDI-TOF MS studies were carried as per our previous report. , The detailed procedure for this is already described in Section S2 in the Supporting Information.…”

“…The DCFDA assay was performed as per our previous reports with slight modification. 22,27 The detailed procedure is given in the Supporting Information (Section S7).…”

Protein-Cloaked Nanoparticles for Enhanced Cellular Association and Controlled Pathophysiology via Immunosurveillance Escape

“…32,33 For evaluating the oxidative stress levels of cells due to bare and proteincloaked NPs, intracellular reactive oxygen species (ROS) estimation was performed as described earlier. 32,33 Further, for the direct visualization of the ROS generation, fluorescence microscopic analysis was performed for bare and protein-cloaked FITC-conjugated NPtreated cells. For assessing the internalization of bare and proteincloaked NPs inside the cells under in vitro conditions, cellular internalization studies were carried out on cell lines, viz., HEK-293 and human adenocarcinomic alveolar basal epithelial cells (A549).…”

“…For cell viability studies of the bare and protein-cloaked NPs, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out using human embryonic kidney (HEK-293) cells following our previous protocol with minor modifications. , For evaluating the oxidative stress levels of cells due to bare and protein-cloaked NPs, intracellular reactive oxygen species (ROS) estimation was performed as described earlier. , Further, for the direct visualization of the ROS generation, fluorescence microscopic analysis was performed for bare and protein-cloaked FITC-conjugated NP-treated cells. For assessing the internalization of bare and protein-cloaked NPs inside the cells under in vitro conditions, cellular internalization studies were carried out on cell lines, viz.…”