Nanozymes: modulators of neural cells

在过去的五年里，我们在神经细胞纳米结构的使用和行为方面完成了令人兴奋的研究，这促使我们提出了纳米酶的研究。为什么是纳米酶？纳米酶是一种模仿酶活性的纳米结构。它们被认为是下一代人工酶，由于其稳定性、独特的表面性质和低生产成本，一直是多学科研究的热点。尽管如此，由于它们作为纳米工具和纳米传感器的广泛应用，许多性能仍然可以改进。我们的假设是，特定形状、大小和表面配体的金纳米簇(AuNC)纳米酶将微调人类细胞中的氧化还原调节酶，从而维持被脂毒素破坏的动态平衡。我们的长期目标是揭示AuNC上的哪些表面配体促进或消除暴露于高脂肪食物中的脂毒素的神经胶质细胞有益的氧化还原变化，这些脂肪毒素来自高水平的饱和酸(例如棕榈酸和过氧化不饱和酸)。我们特别感兴趣的是几个关键的信号转导途径，以揭示纳米酶(单独或与选定的信号分子调节器结合)可以被评估的步骤。该实验方法适用于多种细胞类型和氧化还原调节剂以外的其他酶系统。我们的目标是通过将纳米酶与少量的天然酶或小核仁RNA(SnoRNA)相结合来改善细胞的生理功能。我们的短期目标是：1.确定哪些配体可以最好地提高氧化还原酶活性(过氧化氢酶、过氧化物酶、歧化酶、硫氧还蛋白还原酶)；2.产生将纳米酶与天然酶相结合的集成纳米酶(INAzymes)，从而提高有益的酶活性；3.证明纳米酶和INAzyme在人类细胞模型中是有效的，包括暴露在各种伤害下的神经细胞。金纳米团簇有精确数量的原子排列在特定的空间位置。我们建议研究具有10到25个金原子的AuNC，因为它们被很好地表征。可以对它们的表面进行修饰，以提高其酶活性，并将毒性降至最低或消除。意义重大。我们的结果将展示为什么以及如何在不同的应激条件下，包括富含饱和脂肪酸的食物及其代谢产物引起的情况下，金纳米簇可以改变人类细胞的氧化还原状态。AUNC的生产和处理是环保和具有成本效益的。对于对纳米结构在细胞水平上的影响感兴趣的不同水平的学生来说，拟议的研究是一个很好的培训平台，不仅在细胞水平上，而且在各种侮辱和相关的氧化还原损伤之后也是如此。

The exciting studies we completed in the last five years on the use and behavior of nanostructures with neural cells have led us to propose studies on nanozymes. Why nanozymes? Nanozymes are nanostructures that mimic enzymatic activities. They are considered the next generation of artificial enzymes and have been of high interest for multidisciplinary investigations due to their stability, unique surface properties and low cost of production. Still, many properties can be improved for their wide application as nanotools and nanosensors. Our hypothesis is that gold nanocluster (AuNC) nanozymes of selected shapes, sizes and surface ligands will fine-tune redox-regulating enzymes in human cells, thereby maintaining homeostasis disrupted by lipotoxins. Our long-term objective is to uncover which surface ligands on AuNC promote or abolish beneficial redox changes in glial cells exposed to lipotoxins from high-fat food containing high levels of saturated acids (e.g. palmitic acid and peroxidized unsaturated acids). We are particularly interested in several key signal transduction pathways to reveal the steps at which nanozymes (alone or combined with selected modulators of signaling molecules) can be assessed. The experimental approaches are applicable to many cell types and other enzymatic systems beyond redox regulators. We aim to improve physiological cell functions by combining nanozymes with small amounts of natural enzymes or small nucleolar RNA (snoRNA). Our short-term objectives are: 1. to establish which ligands can best improve redox enzymatic activity (catalase, peroxidase, dismutase, thioredoxin reductase); 2. to generate integrated nanozymes (INAzymes) combining nanozymes with natural enzymes, thereby enhancing beneficial enzymatic activity and 3. to show that nanozymes and INAzymes are effective in human cell models, including neural cells exposed to various insults. Gold nanoclusters have a precise number of atoms arranged in specific spatial locations. We propose to study AuNC with 10 to 25 gold atoms because they are well characterized. Their surfaces can be modified to improve their enzymatic activities and minimize or eliminate toxicity. Significance. Our results will show why and how gold nanoclusters can alter redox status in human cells under different stressful conditions, including those caused by food rich in saturated fatty acids and their metabolic products. The production and handling of AuNC are environmentally-friendly and cost effective. The proposed studies are an excellent training platform for students at different levels interested in the effects of nanostructures at the cellular level, not only in metaflammation but also following diverse insults and associated redox impairments.