School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave., Milwaukee, WI 53204, United States.
Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD 21250, United States.
NanoImpact. 2021 Apr;22:100318. doi: 10.1016/j.impact.2021.100318. Epub 2021 Apr 19.
Surface properties of engineered nanomaterials (ENMs) have been shown to influence their interaction with biological systems. However, studies to date have largely focused on hydrophilic materials, likely due to biocompatibility concerns and aqueous exposure conditions necessary for many model systems. Therefore, a knowledge gap exists in nanotoxicity literature for impacts of hydrophobic ENMs, with studies of hydrophobic materials largely limited to carbon ENMs. Here we demonstrate testing of hydrophobic quantum dots (QDs) using the nematode C. elegans, a model soil organism cultured on solid media and amenable to hydrophobic exposures. To evaluate the influence of hydrophobicity, we compared CdSe/ZnS QDs functionalized with hydrophobic trioctylphosphine oxide (TOPO) to identical QDs functionalized with hydrophilic dihydrolipoic acid-polyethylene glycol (DHLA-PEG) and alternative hydrophobic CdSe/ZnS QDs functionalized with oleic acid (OA). Results show that hydrophobic TOPO QDs are significantly more toxic than hydrophilic DHLA-PEG QDs, and substitution of TOPO with OA yields relatively non-toxic hydrophobic QDs. Fluorescence microscopy shows TOPO QDs loosely associated with the organism's cuticle, but atomic force microscopy shows no difference in cuticle structure from exposure. Importantly, TOPO ligand alone is as toxic as TOPO QDs, and our data suggests that TOPO may impact neuromuscular function, perhaps upon displacement from the QD surface. This study demonstrates the importance of examining ligand-specific impacts of hydrophobic ENMs and indicates OA-functionalized QDs as a potential alternative to TOPO QDs for reduced toxicity.
工程纳米材料（ENMs）的表面性质已被证明会影响它们与生物系统的相互作用。然而，迄今为止的研究主要集中在亲水材料上，这可能是由于生物相容性问题以及许多模型系统所需的水暴露条件。因此，在纳米毒性文献中，对于疏水性 ENMs 的影响存在知识空白，而对疏水性材料的研究主要限于碳 ENMs。在这里，我们使用线虫 C. elegans 展示了疏水性量子点（QD）的测试，这是一种在固体培养基上培养的模式土壤生物，适合疏水性暴露。为了评估疏水性的影响，我们将用三辛基氧化膦（TOPO）官能化的 CdSe/ZnS QD 与用亲水性二氢硫辛酸-聚乙二醇（DHLA-PEG）官能化的相同 QD 以及用油酸（OA）官能化的替代疏水性 CdSe/ZnS QD 进行了比较。结果表明，疏水性 TOPO QD 比亲水性 DHLA-PEG QD 毒性大得多，用 OA 取代 TOPO 可得到相对无毒的疏水性 QD。荧光显微镜显示 TOPO QD 与生物体的角质层松散结合，但原子力显微镜显示角质层结构没有因暴露而发生变化。重要的是，TOPO 配体本身与 TOPO QD 一样具有毒性，我们的数据表明 TOPO 可能会影响神经肌肉功能，也许是在从 QD 表面置换后。这项研究表明了研究疏水性 ENMs 中配体特异性影响的重要性，并指出 OA 官能化的 QD 是降低毒性的 TOPO QD 的潜在替代品。
