Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, OH 44325, United States.
J Colloid Interface Sci. 2017 Nov 1;505:973-982. doi: 10.1016/j.jcis.2017.06.093. Epub 2017 Jun 29.
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.
阿尔茨海默病的特征是淀粉样 β 蛋白（Aβ）纤维在人脑中的积累，金属离子（如 Zn）的结合与 Aβ的聚集和细胞毒性密切相关。在这里，我们设计并合成了亚氨基二乙酸偶联的纳米粒子（IDA-NP），以调节 Aβ聚集并降低 Zn 加速的细胞毒性。结果表明，IDA-NP 具有高金属螯合容量（752μmol/g）和对 Aβ纤维化的有效抑制能力。Zn 离子可通过与 IDA-NP 螯合而被完全去除，从而导致 Aβ纤维的恢复。然后，IDA-NP 的特殊表面特性抑制了 Aβ的纤维化。结果，IDA-NP 保护了 SH-SY5Y 细胞免受 Zn-Aβ 诱导的细胞毒性，细胞活力增加了约 80%（从 47.6%增加到 86.3%）。研究证明，IDA-NP 是一种有效的双功能纳米调节剂，可预防 Zn 介导的 Aβ聚集和细胞毒性。
