Iminodiacetic acid-conjugated nanoparticles as a bifunctional modulator against Zn2+-mediated amyloid β-protein aggregation and cytotoxicity

Abstract

Alzheimer's disease is characterized by the accumulation of amyloid β-protein (Aβ) fibrils in human brain, and the binding of metal ions, such as Zn²⁺, is closely associated with the aggregation and cytotoxicity of Aβ. Here, we designed and synthesized iminodiacetic acid-conjugated nanoparticles (IDA-NP) to modulate Aβ₄₂ aggregation and reduce the cytotoxicity accelerated by Zn²⁺. Results showed that IDA-NP enabled high metal-chelate capacity (752μmol/g) and potent inhibition capability against Aβ₄₂ fibrillation. Zn²⁺ ions could be completely removed by chelating to IDA-NP, which leads to the recovery of on-pathway Aβ₄₂ fibrillation. Then, the special surface character of IDA-NP inhibited Aβ₄₂ fibrillation. As a result, IDA-NP protected SH-SY5Y cells from the cytotoxicity induced by Zn²⁺-Aβ₄₂ species, as evidenced by about 80% (from 47.6% to 86.3%) increase of the cell viability. The research proved that IDA-NP was a potent bifunctional nano-modulator for preventing Zn²⁺-mediated Aβ aggregation and cytotoxicity.

Keywords: Aggregation; Amyloid β-protein; Inhibitor; Metal chelator; Nanoparticle.