Hydroxylated Single-Walled Carbon Nanotubes Inhibit Aβ₄₂ Fibrillogenesis, Disaggregate Mature Fibrils, and Protect against Aβ₄₂-Induced Cytotoxicity

Abstract

The fibrillogenesis of amyloid-β protein (Aβ) is considered a crucial factor in the pathogenesis of Alzheimer’s disease (AD). Hence, inhibiting Aβ fibrillogenesis is regarded as the primary therapeutic strategy for the prevention and treatment of AD. However, the development of effective inhibitors against Aβ fibrillogenesis has faced significant challenges. Previous studies have shown that pristine single-walled carbon nanotubes (SWNTs) can inhibit fibrillogenesis of some amyloid proteins. However, the poor dispersibility of SWNTs in an aqueous environment greatly hinders their inhibitory efficacy. Here, we examined the inhibitory activity of hydroxylated SWNTs (SWNT-OH) on the aggregation and cytotoxicity of Aβ42 using thioflavin T (ThT) fluorescence, atomic force microscopy (AFM), cellular viability assays, and molecular dynamics (MD) simulations. ThT and AFM results showed that SWNT-OH inhibits Aβ42 fibrillogenesis and disaggregates preformed amyloid fibrils in a dose-dependent manner. Furthermore, the ratio of hydroxyl groups in SWNT-OH is crucial for their effect against Aβ42 aggregation. SWNT-OH exerted cytoprotective effects against Aβ42 fibrillation-induced cytotoxicity. The results of free-energy decomposition studies based on MD simulations revealed that nonpolar interactions, and especially van der Waals forces, contributed most of the free energy of binding in the SWNT-OH–Aβ complex. Two regions of the Aβ pentamer were identified to interact with SWNT-OH, spanning H13–Q15 and V36–G38. The findings presented here will contribute to a comprehensive understanding of the inhibitory effect of hydroxylated nanoparticles against Aβ fibrillogenesis, which is critical for the search for more effective agents that can counteract amyloid-mediated pathologies.

Nitrogen‐Doped Carbonized Polymer Dots: A Potent Scavenger and Detector Targeting Alzheimer's β‐Amyloid Plaques

“…Aβ 40 (25 µm) was incubated with CPDs (1, 10, and 100 µg mL nanosheet could disassemble the preformed Aβ-Cu 2+ aggregates in 4 h, and graphene oxide/graphitic carbon nitride (GO/g-C 3 N 4 ) could photodegrade the aggregates of Aβ (33)(34)(35)(36)(37)(38)(39)(40)(41)(42) under UV after 100 min incubation. [63,64] Hydroxylated single-walled carbon nanotubes (SWCN-OH) significantly remodeled the Aβ 42 fibrils into small granular aggregates with the treatment for 5 h. [65] Photoactivated branched polyethylenimine-coated carbon nanodots (bPEI@CDs) distinctively facilitated the dissolution and disruption of β-sheet-rich Aβ fibrils to soluble species in 2 d. [66] Compared with the above literature data, CPDs significantly disintegrated the long and dense β-sheet rich Aβ fibrils to amorphous aggregates in 10 min, showing a high potency in the disassembly of preformed Aβ fibrils in a time scale of seconds to minutes (Figure 3c). We speculate that electrostatic interactions, H-bonding and hydrophobic interactions by the positively charged free amino groups and the skeleton of conjugated aromatic structures composed of pyrimidine rings, pyrrole rings, and benzene rings are the keys to the rapid remodeling potency of CPDs.…”

Nanochaperone‐Based Strategies to Control Protein Aggregation Linked to Conformational Diseases

“…Similarly, surface‐hydroxylated single‐walled carbon nanotubes (SWNTs) can inhibit Aβ42 fibrillogenesis and disaggregate mature fibrils in a dose‐dependent manner. The interaction occurs via both hydrophobic and electrostatic forces [74] . Molecular‐dynamics simulations on SWNTs‐Aβ(16–22) interactions in water concluded that hydrophobic and mostly, π‐stacking interactions with Phe residues prevent β‐sheet formation and destabilize prefibrillar β‐sheets [75] …”

“…The interaction occurs via both hydrophobic and electrostatic forces. [74] Molecular-dynamics simulations on SWNTs-Ab (16)(17)(18)(19)(20)(21)(22) interactions in water concluded that hydrophobic and mostly, p-stacking interactions with Phe residues prevent b-sheet formation and destabilize prefibrillar b-sheets. [75] Low surface energy is gained by proteins adsorbed on hydrophilic surfaces.T his effect is commonly exploited by covering surfaces with sterically demanding or polar polymers like polyethylene glycol (PEG).…”

New Nanostructured Carbon Coating Inhibits Bacterial Growth, but Does Not Influence on Animal Cells

“…MWCNTs are considered potentially effective against Alzheimer's disease [10]. This is likely due to the ability of MWCNTs to inhibit Aβ42 fibrillogenesis, as well as to disaggregate mature fibrils, which protects the body from cytotoxicity induced by Aβ42 [11]. It should be noted that fullerenes and carbon nanotubes are actively used not only for the treatment of neurodegenerative diseases, but also for their diagnostics [12].…”