Nanozymes: modulators of neural cells

纳米酶：神经细胞的调节剂

• 批准号: RGPIN-2020-07011
• 负责人: Maysinger, Dusica
• 金额: $ 3.06万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=762103
• 关键词: Nanozymes; modulators; neural; cells

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.

在过去的五年里，我们完成了关于纳米结构与神经细胞的使用和行为的令人兴奋的研究，这使我们提出了关于纳米酶的研究。为什么是纳米酶？纳米酶是模拟酶活性的纳米结构。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而受到多学科研究的高度关注。尽管如此，许多性能可以改善其广泛的应用，如纳米工具和纳米传感器。我们的假设是，选定形状，大小和表面配体的金纳米簇（AuNC）纳米酶将微调人体细胞中的氧化还原调节酶，从而维持被脂毒素破坏的体内平衡。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含有高水平饱和酸（例如棕榈酸和过氧化不饱和酸）的高脂肪食物中的脂毒素的神经胶质细胞中的有益氧化还原变化。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剂组合）可以评估的步骤。实验方法适用于许多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天然酶或小核仁RNA（snoRNA）结合来改善生理细胞功能。我们的短期目标是：1。确定哪些配体可以最好地改善氧化还原酶活性（过氧化氢酶、过氧化物酶、歧化酶、硫氧还蛋白还原酶）; 2.以产生将纳米酶与天然酶组合的整合纳米酶（INAzymes），从而增强有益的酶活性，以及3.以显示纳米酶和INAzymes在人类细胞模型中是有效的，包括暴露于各种损伤的神经细胞。金纳米团簇具有排列在特定空间位置的精确数量的原子。我们建议研究具有10至25个金原子的AuNC，因为它们具有很好的特征。它们的表面可以被改性以提高它们的酶活性并最小化或消除毒性。意义我们的研究结果将显示为什么以及如何金纳米团簇可以在不同的压力条件下改变人体细胞的氧化还原状态，包括那些由富含饱和脂肪酸及其代谢产物的食物引起的。AuNC的生产和处理对环境友好且具有成本效益。拟议的研究是一个很好的培训平台，为学生在不同层次感兴趣的纳米结构在细胞水平上的影响，不仅在metaflammation，而且在不同的侮辱和相关的氧化还原损伤。