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

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 Zn, is closely associated with the aggregation and cytotoxicity of Aβ. Here, we designed and synthesized iminodiacetic acid-conjugated nanoparticles (IDA-NP) to modulate Aβ aggregation and reduce the cytotoxicity accelerated by Zn. Results showed that IDA-NP enabled high metal-chelate capacity (752μmol/g) and potent inhibition capability against Aβ fibrillation. Zn ions could be completely removed by chelating to IDA-NP, which leads to the recovery of on-pathway Aβ fibrillation. Then, the special surface character of IDA-NP inhibited Aβ fibrillation. As a result, IDA-NP protected SH-SY5Y cells from the cytotoxicity induced by Zn-Aβ 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 Zn-mediated Aβ aggregation and cytotoxicity.