Collaborative Research: Teasing apart how specific nanoparticle features relate to environmental fate and contribute to ecotoxicity

银纳米颗粒因其抗菌特性在越来越多的消费和商业产品中广泛使用，并作为废水处理中的细菌剂。由于它们的高需求，全球生产了超过500吨的工程纳米银。虽然这些纳米粒子的特性对它们的抗菌活性很重要，但有些也可能影响毒性。银纳米颗粒对环境的影响独立于它们的离子浸出是具有挑战性的。由于银纳米粒子容易发生离子溶解，因此旨在评估其纳米粒子特异性效应的研究受到了限制。此外，由于研究设计的差异，离子对颗粒毒性的相对贡献在文献中仍然普遍存在差异。因此，与粒子效应相比，我们非常需要了解具有不同特性的银纳米粒子是如何通过控制离子对毒性的混淆效应来影响与生物体的相互作用的。该研究人员提出的研究将有助于科学地理解这些纳米颗粒的特性如何在生物吸收、纳米颗粒-生物相互作用和生态毒性中发挥作用。这项研究将涉及消除颗粒表面氧化和离子溶解的影响，这在过去的毒性研究中是复杂的。这一贡献意义重大，因为它将提高我们识别银纳米颗粒破坏生态的特征，并预测这些特征如何导致不利的环境后果的能力。所有数据将通过全球纳米材料-生物相互作用（NBI）的开源知识库共享，用于建模工作，并将支持安全协议、暴露指南和保护人类和生态系统健康的法规的制定。此外，这项研究将为新型银纳米粒子的组装提供设计规则，这些纳米粒子可以商业化，而不必担心粒子的快速降解和释放到环境中。此外，该项目旨在吸收来自不同背景的学生，并将有助于培养未来的科学、技术、工程和数学（STEM）人才。研究人员的总体目标是提高我们对纳米粒子-生物相互作用的具体物理化学特征的理解。首先，他们将设计一系列脂质包覆的银纳米粒子，以不同的方式屏蔽离子溶解。将不同大小和形状的银纳米颗粒包裹在混合脂质膜中，以保护其表面免受氧化和离子溶解，从而制备出差异屏蔽银纳米颗粒。局部表面等离子体共振（LSPR）、热电子显微镜（TEM）和电感耦合等离子体质谱仪（ICP-MS）的变化将被用来监测银离子从纳米颗粒中溶解。其次，他们将确定导致颗粒不稳定的脂质包裹纳米颗粒的特征。利用动态光散射和纳米颗粒跟踪分析来评估杂化脂包覆银纳米颗粒的团聚动力学。第三，由于目标是最终将这些材料特征与纳米颗粒-生物相互作用联系起来，研究人员将确定银纳米颗粒组的吸收和毒性。根据初步研究，具有坚固涂层的杂化脂质包覆银纳米颗粒应引起最小的毒性，而表面覆盖率的减少应导致相应的毒性增加。一项成熟的胚胎斑马鱼试验将用于确定暴露导致的脊椎动物发病率和死亡率，高光谱成像（HSI）将用于可视化整个动物的纳米颗粒摄取。最后，研究人员将使用一种新的纳米宇宙测定法评估该套件的潜在生态毒性。在小规模淡水实验中，高光谱成像将用于可视化纳米颗粒在细菌、藻类、甲壳类动物和鱼类之间的生物分布。总的来说，使用特性良好的银纳米颗粒来调节离子释放，将使pi能够梳理出纳米颗粒和离子对生物吸收、毒性和潜在环境影响的相对贡献。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Silver nanoparticles are extensively used for their antimicrobial properties in an increasing number of consumer and commercial products and as bacterial agents in the treatment of wastewater. Because of their high demand, over 500 tons of engineered silver nanoparticles are produced globally. While the properties of these nanoparticles are important for their antibacterial activity, some may also influence toxicity. The environmental impacts of silver nanoparticles independent of their ion leaching are challenging at best. Studies designed to evaluate the nanoparticle-specific effects of silver nanoparticles have been limited because of their propensity to undergo ionic dissolution. Furthermore, discrepancies over the relative contribution of ion to particle toxicity remain prevalent in the literature primarily due to differences in study design. Consequently, there is a great need to understand how silver nanoparticles with diverse characteristics impacts the interaction with organisms by controlling for the confounding effects of ionic contribution to toxicity as compared to particle effects. The researcher's proposed studies will contribute to the scientific understanding of how the properties of these nanoparticles play a role in biouptake, nanoparticle-biological interactions, and ecotoxicity. The research will involve the elimination of the effects of particle surface oxidation and ionic dissolution, which has complicated toxicity studies in the past. This contribution is significant because it will improve our ability to identify features of silver nanoparticles that make them eco-disruptive and predict how these features lead to adverse environmental outcomes. All data will be shared through the open-source knowledge base of Nanomaterial-Biological Interactions (NBI) globally for modeling efforts and will support the development of safety protocols, exposure guidelines, and regulations that protect human and ecosystem health. Furthermore, this research will provide design rules for the assembly of new classes of silver nanoparticles that could be commercialized without concern regarding rapid particle degradation and release into the environment. In addition, this project is designed to incorporate students from diverse backgrounds and will help build future science, technology, engineering and math (STEM) talent. The researcher's overall aim is to improve our understanding of the specific physiochemical features that dictate nanoparticle-biological interactions. First, they will design a series of lipid-coated silver nanoparticles that are differentially shielded from ion dissolution. Differentially shielded silver nanoparticles will be prepared by encapsulating silver nanoparticles of varying size and shape with a hybrid lipid-membrane to protect the surface from oxidation and ionic dissolution. Changes in the localized surface plasmon resonance (LSPR), thermal electron microscope (TEM), and (Inductively-coupled plasma mass spectrometer (ICP-MS) will be employed to monitor silver ion dissolution from the suite of nanoparticles. Second, they will identify features of lipid-coated nanoparticles that lead to particle instability. The agglomeration kinetics of the hybrid lipid-coated silver nanoparticles will be assessed using dynamic light scattering and nanoparticle tracking analysis. Third, since the goal is to ultimately relate these material features with nanoparticle-biological interactions, the researchers will determine the uptake and toxicity of the silver nanoparticle suite. Based on preliminary investigations, the hybrid lipid-coated silver nanoparticles with a robust coating should elicit minimal toxicity and a decrease in surface coverage should lead to a respective increase in toxicity. A well-established embryonic zebrafish assay will be used to identify vertebrate morbidity and mortality resulting from exposure and hyperspectral imaging (HSI) will be used to visualize nanoparticle uptake in whole animals. Finally, the researchers will assess the potential ecotoxicity of the suite using a novel nanocosm assay. Hyperspectral imaging will be used to visualize nanoparticle biodistribution among bacteria, algae, crustaceans, and fish in the small-scale freshwater assay. Collectively, the use of well-characterized silver nanoparticles tuned for ion release will allow the PIs to tease apart the relative contribution of the nanoparticle and ion to biouptake, toxicity, and potential for environmental impacts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.