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  • Recently different kinds of A aggregation inhibitors have be

    2023-12-01

    Recently, different kinds of Aβ aggregation inhibitors have been reported, including small molecules [8], peptides [9], and nanoparticles (NPs) [10]. The working mechanisms of the inhibitors are mostly to bind or adsorb Aβ molecules and to affect the conformational changes followed by blocking the aggregation [8]. Thus, nanoparticle cetyltrimethylammonium bromide inhibitors have received special attention because they possess high specific surface area, unique structural superiority, ease of surface functionalization and modification [11]. Several NPs including polymers [12], gold (Au) [13], and Polysaccharide-coated NPs [14], have been used to prevent Aβ fibrillogenesis. Previous studies have suggested that the surface charge and hydrophobicity of NPs played important roles in the interactions between Aβ and NPs. Aβ has six acidic amino cetyltrimethylammonium bromide residuals, three basic amino acid residuals and three His residuals (Fig. S1), so it has an isoelectric point of 5.5 and carries net negative charges under physiological conditions [15]. However, under physiological conditions it still possesses positively charged areas which affect the aggregation process [16,17]. The electrostatic interactions between the charged amino acid residuals of Aβ also greatly influence the aggregation process [18,19]. Hence, it is reasonable that many studies have indicated that charged NPs and macromolecules affect Aβ aggregation. Obviously, the surface charge of NPs or macromolecules is a key factor influencing Aβ aggregation. However, there exists distinct controversy about the effects of charge properties of NPs or macromolecules on Aβ aggregation. For example, some studies indicated that positively charged NPs inhibited Aβ fibrillogenesis [20,21], and the inhibition effect was explained by the tight electrostatic interaction between NPs and Aβ, because it might decrease free Aβ species or interfere with the process of Aβ fibrillogenesis [22]. However, some other studies indicated that some positively charged NPs or macromolecules did not inhibit Aβ aggregation or even promoted Aβ aggregation [13,23,24]. A similar discrepancy can be found in literature with negatively charged NPs. Some studies indicated that negative charges had more effective suppressing effects on Aβ aggregation [[25], [26], [27]], while others demonstrated that negative charges did not inhibit aggregation [28,29]. For instance, citrate-coated AuNPs showed opposite effects on Aβ aggregation in different literature [13,29]. From the literature, we found two points that should be noted. (1) Surface hydrophobicity of NPs is also an important factor influencing Aβ aggregation, as demonstrated by a lot of studies [30]. (2) The inhibition or promotion effect of charged NPs or macromolecules changes with pH or for different Aβ species. In the literature, it was clear that the NPs used had different surface hydrophobicities and/or the conditions used by different researchers for the NPs preparation and/or Aβ aggregation were not completely the same. The discrepancies would cause the contradictory results considering the sensitivity of Aβ aggregation [31]. Polysaccharide nanocomposites have become increasingly important materials over the past decade with the merits of antibacterial and stable property [32,33]. Hence, this work is designed to systematically study the effect of surface charge on Aβ aggregation by using a series of NPs with similar surface hydrophobicities but different surface charges. The NPs were prepared by the self-assembly of chitosan (CS) and hyaluronic acid (HA). CS and HA are respectively positively and negatively charged polysaccharides, so they can self-assemble into composite CS-HA (CH) NPs via electrostatic interactions (Fig. S2) [34,35]. Solution pH affects the net charge of Aβ and has a great impact on amyloid protein aggregations [[36], [37], [38]]. Therefore, the effects of CH NPs on Aβ aggregation were studied at different pH conditions to provide more insights into the working mechanisms of surface charges.