The effect of mesoporous silica nanoparticle surface chemistry and concentration on the α-synuclein fibrillation

Abstract

The aggregation of an amyloid protein, a-synuclein (a-Syn), has been suggested as a potential cause of Parkinson's and several other neurodegenerative diseases. To explore the possibility of using nanoparticle-based therapeutic agents for the treatment of such diseases, we investigated the influence of surface chemistry and concentration of mesoporous silica nanoparticles (MSNPs) on the fibrillation of recombinant human a-Syn protein in the present work. Bare MSNPs as well as MSNPs of different surface functionalities, including 3-(2-aminoethyl amino) propyltrimethoxysilane (AAS), succinic anhydride (carboxyl), and polyethyleneimine (PEI) were prepared and characterized by electron microscopy, zeta potential measurement, Brunauer-Emmett-Teller (BET) isotherms, and FT-IR analyses.The process of a-Syn fibril formation was monitored by Thioflavin T (ThT) assay, atomic force microscopy (AFM) and fluorescence microscopy imaging. The conformation of a-Syn molecules in fibrillar forms and upon adsorption onto MSNPs was investigated by circular dichroism (CD) analysis, and an MTT assay was employed to evaluate the cytotoxicity effects of a-Syn fibrils on a PC12 cell line in the absence and presence of MSNPs. The synthesized MSNPs were spherical and monodisperse with an average size of 83 AE 6 nm. Our results showed that the fibril formation is reduced considerably in the presence of positively-charged MSNPs, i.e. AAS-and PEI-MSNPs, and is enhanced while treated with negatively-charged MSNPs, i.e. bare and carboxyl-MSNPs. Furthermore, it was also demonstrated that increasing the concentration of the MSNPs regardless of their surface chemistry results in greater effects on the fibril formation-promoting or inhibiting for negatively and positively-charged MSNPs respectively. Subsequently, the cytotoxicity of the formed aggregates was noticed to be significantly reduced in the presence of AAS-and PEI-MSNPs in comparison to that in the absence of these MSNPs.These results suggest that the electrostatic charges and concentration of MSNPs play important regulatory roles in the fibrillation process of a-Syn. Thus, the present study contributes towards the better understanding and control of protein fibrillation by nanoparticles which can lead to development of nanoparticle-mediated therapies.

Stability and Antimicrobial Activity of Nisin-Loaded Mesoporous Silica Nanoparticles: A Game-Changer in the War against Maleficent Microbes

“…This is due to the fact that DLS analysis measures the hydrodynamic size of the particles, which is usually larger than the actual size of the particles. The mean pore diameter and specific surface area as measured in our previous studies 27,30,35 , are 4.1 nm and 882.1 m 2 g -1 , respectively. In those works, it was shown that the as-prepared MSNs present a structure of MCM-41 27,30,35 , which have channel-like pores 26 .…”

“…The MSNs were prepared and functionalized according to a previously reported approach based on the template removing method 30 . In brief, 100 mg of CTAB and 350 µL of sodium hydroxide aqueous solution (2 M) were added to 48.65 mL of water at 80 o C with constant stirring.…”

Cuminaldehyde as the Major Component of Cuminum cyminum, a Natural Aldehyde with Inhibitory Effect on Alpha‐Synuclein Fibrillation and Cytotoxicity

“…The results of fluorescence microscopy are also demonstrated in Figure D. Samples containing fibrils are almost transparent in visible light; however, by coloring with ThT, fibrils can be seen and identified under the fluorescence microscope as extended particles (Ban and Goto, ; Taebnia and others ). Extended particles were observed in the fluorescence images of both untreated samples and those treated with spermidine, while only small and dispersed particles could be seen in the fluorescence images of the sample incubated in the presence of cuminaldehyde (Figure D).…”

The Antiaggregative and Antiamyloidogenic Properties of Nanoparticles: A Promising Tool for the Treatment and Diagnostics of Neurodegenerative Diseases

“…A plethora of evidence suggests that the nanostructures can influence protein fibrillation depending on various conditions, including the coating, size, surface charge, and concentration. Such discrepancy has been seen for example in silica-based nanoparticles, where positively charged silica nanoparticles inhibited α -syn fibrillation and negatively charged one had an opposite effect [ 67 ]. Also, it was also established that SiO 2 NPs upregulate α -syn expression, inhibit protein levels of the ubiquitin-proteasome system, and induce autophagy by interference in the PI3K-Akt-mTOR signalling pathway [ 68 ].…”