Toxicity of polymer-modified CuS nanoclusters on zebrafish embryo development
Toxicity of polymer-modified CuS nanoclusters on zebrafish embryo development
复制标题
聚合物修饰的 CuS 纳米团簇对斑马鱼胚胎发育的毒性
DOI：
10.1002/jat.4217
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发表时间：
2021-07-11
影响因子：
3.3
通讯作者：
Chen，Dongyan
中科院分区：
文献类型：
--
作者：
Zhang，Qiuping;Wang，Lifeng;Chen，Dongyan
尽管对铜基纳米颗粒的毒性进行了大量研究，但 CuS 纳米颗粒的毒性仍然很大程度上未知。由于CuS基纳米材料在生物医学工程中的应用，有必要研究其潜在的毒性和生物效应。在本研究中，我们通过在受精后 0.75 小时将斑马鱼胚胎暴露于 1、2.5、5、7.5 和 10 mg/L PATA3-C4@CuS 中，评估了聚合物修饰的 CuS 纳米团簇 (PATA3-C4@CuS) 对胚胎发育的毒性。形态学结果表明，浓度大于 1 mg/L 的 PATA3-C4@CuS 会诱导异常表型，包括头部和眼睛变小、心包水肿和胚胎发育迟缓，并增加死亡率、降低孵化率并抑制鱼鳔充气。原位杂交和定量逆转录聚合酶链反应表明，PATA3-C4@CuS可以改变tbxta、dlx3和cstl的表达模式，增加wnt5和wnt11的表达水平，这表明PATA3-C4@CuS通过增加原肠胚形成过程中wnt5和wnt11的水平来破坏细胞迁移。研究还发现，PATA3-C4@CuS 暴露会导致斑马鱼幼虫心率减慢和心室变小。免疫荧光和行为分析表明，PATA3-C4@CuS 会损害初级运动神经元 CaP 的腹侧投射，这与运动能力的降低相符。总之，我们的数据表明，功能性 PATA3-C4@CuS 可以破坏原肠胚形成过程中的细胞迁移，影响心脏发育和功能，并降低运动活动。
Despite the vast amount of research on the toxicity of copper‐based nanoparticles, the toxicity of CuS nanoparticles is still largely unknown. Due to the application of CuS‐based nanomaterials in biomedical engineering, it is necessary to study their potential toxicity and biological effects. In this study, we evaluated the toxicity of polymer‐modified CuS nanoclusters (PATA3‐C4@CuS) on embryo development through exposing zebrafish embryos to 1, 2.5, 5, 7.5, and 10 mg/L PATA3‐C4@CuS at 0.75‐h post‐fertilization. The morphological results demonstrated that PATA3‐C4@CuS at concentrations greater than 1 mg/L PATA3‐C4@CuS induced abnormal phenotypes including smaller heads and eyes, pericardial edema, and epiboly retardation and it increased mortality, lowered the hatching rate, and inhibited swim bladder inflation. In situ hybridization and quantitative reverse transcription polymerase chain reaction showed that PATA3‐C4@CuS could alter the expression patterns oftbxta,dlx3, andcstlband increase the expression levels ofwnt5andwnt11, which suggested that PATA3‐C4@CuS disrupts cell migration by increasing the levels ofwnt5andwnt11during gastrulation. It was also discovered that PATA3‐C4@CuS exposure caused a slow heart rate and smaller ventricles in zebrafish larvae. Immunofluorescence and behavioral analyses showed that PATA3‐C4@CuS could damage the ventral projection of the primary motor neurons CaP, which was in accordance with the reduction in locomotion ability. Together, our data demonstrated that functional PATA3‐C4@CuS could disrupt cell migration during gastrulation, affect cardiac development and function, and decrease locomotive activity.