Alzheimer's disease is characterized by the accumulation of amyloid beta-protein (AO) fibrils in human brain, and the binding of metal ions, such as Zn2+, is closely associated with the aggregation and cytotoxicity of Ap. Here, we designed and synthesized iminodiacetic acid-conjugated nanoparticles (IDA-NP) to modulate A beta(42) aggregation and reduce the cytotoxicity accelerated by Zn2+. Results showed that IDA-NP enabled high metal-chelate capacity (752 mu mol/g) and potent inhibition capability against A beta(42) fibrillation. Zn2+ ions could be completely removed by chelating to IDA-NP, which leads to the recovery of on-pathway A beta(42) fibrillation. Then, the special surface character of IDA-NP inhibited A beta(42) fibrillation. As a result, IDA-NP protected SH-SY5Y cells from the cytotoxicity induced by Zn2+-A beta(42) 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 A beta aggregation and cytotoxicity. (C) 2017 Elsevier Inc. All rights reserved.