BIO Fe-antibiotic Hydrogels as a Novel Antibiotic Treatment against Gram-Negative Bacteria

BIO Fe-抗生素水凝胶作为治疗革兰氏阴性菌的新型抗生素

• 批准号: 2587292
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2587292
• 关键词: BIO; Fe; antibiotic; Hydrogels; Novel

From the knowledge I have gained from my degree and additional work, I hope to conduct research into the generation and application of substances with the potential to act as nanoantibiotics. Nanomaterials, such as silver (Ag), have already been used in wound dressings and as linings in reusable shopping bags due to their antimicrobial properties, whilst nanomaterials in general are thought to use different mechanisms in order to inflict bacterial death. Ag is just one nanomaterial which is known to have these characteristics, although others, such as copper, zinc oxide, titanium and silica, are also considered to share this exploitable feature. It has also been suggested that nanomaterials may have lower toxicity levels associated with their use, in comparison to other novel therapies also considered to be future antibacterial alternatives. In considering this, nanomaterials' clinical usage could be more favourable than other substances which could have more severe off- target toxicities.The antibacterial properties possessed by nanomaterials make them an attractive alternative to the clinical (and potentially environmental) use of antibiotics. My intention is to compare the antibacterial activity and tendencies of standard antibiotics to nanomaterials (those previously described as being antibacterial) and nanomaterials conjugated with iron (Fe). Fe is an essential micronutrient which bacteria require to be pathogenic (that being disease-causing) and in order to make more bacterial progeny. By conjugating each nanomaterial with Fe there is the potential to increase nanomaterial delivery to bacteria alongside possible enhanced antibacterial effect. The concept of this project focusses on using the nanomaterial-Fe conjugations to target bacteria currently considered the most problematic to humans; those with several known antibiotic resistances.For a novel therapy to eventually be used clinically, it is important to understand the effects which substances might have on the human system. This project aims to take this into account, by incorporating mammalian cells into experiments. This is crucial to involve in order to gain insight into potential side effects associated with toxicity, providing meaningful conclusions, those which are relevant physiologically, to be made concerning their future clinical use. Moreover, by using a cell line, such as Caco-2 cells, this will reduce the requirement for animals in research which can be wasteful and unethical in addition to not requiring Home Office approval which would be required for use of animals and also experimentation on primary cells.By investigating the minimum inhibitory concentration (MIC) (the lowest concentration of a substance required to stop bacterial growth), this can give an indication of the efficacy of each treatment condition (antibiotic, nanomaterial alone or nanomaterial-Fe conjugation). It would be expected that bacteria with known resistances would have a lower MIC when treated with nanomaterial and nanomaterial-Fe conjugation, in comparison to antibiotic if the nanomaterials are able to exert their antibacterial properties. Whilst, nanomaterial-Fe conjugation may aide the delivery of nanomaterial to bacteria, as these organisms have several mechanisms aiding the uptake and movement of Fe from the bacterium's external environment, across the cell envelope, and into the internal region of the cell, the periplasm.

从我的学位和额外的工作中获得的知识，我希望对具有作为纳米抗生素潜力的物质的产生和应用进行研究。纳米材料，如银(Ag)，由于其抗菌性能，已经被用于伤口敷料和可重复使用的购物袋的衬里，而纳米材料通常被认为使用不同的机制来造成细菌死亡。银只是一种已知具有这些特征的纳米材料，尽管其他材料，如铜、氧化锌、钛和二氧化硅也被认为具有这种可开发的特征。还有人提出，与其他也被认为是未来抗菌替代品的新疗法相比，纳米材料与其使用相关的毒性水平可能较低。考虑到这一点，纳米材料的临床应用可能比其他可能有更严重的非靶标毒性的物质更有利。纳米材料所具有的抗菌特性使其成为临床(以及潜在的环境)抗生素使用的有吸引力的替代方案。我的目的是将标准抗生素的抗菌活性和趋势与纳米材料(那些以前被描述为抗菌的)和与铁(Fe)结合的纳米材料进行比较。铁是一种必需的微量营养素，细菌需要铁才能致病(致病)，才能产生更多的细菌后代。通过将每种纳米材料与铁结合，有可能增加纳米材料对细菌的输送，同时可能增强抗菌效果。这个项目的概念集中在使用纳米材料-铁的结合物来靶向目前被认为对人类最有问题的细菌；那些具有几种已知的抗生素耐药性的细菌。为了最终用于临床的新疗法，了解物质可能对人体系统的影响是重要的。该项目旨在通过将哺乳动物细胞纳入实验来考虑这一点。这是至关重要的，为了深入了解与毒性相关的潜在副作用，提供有意义的结论，这些结论与生理相关，将就其未来的临床应用做出决定。此外，通过使用细胞系，如Caco-2细胞，这将减少对动物研究的要求，这些研究可能是浪费和不道德的，而且不需要获得内政部的批准，使用动物和在原代细胞上进行实验。通过研究最低抑制浓度(MIC)(阻止细菌生长所需的物质的最低浓度)，这可以指示每种治疗条件(抗生素、单独纳米材料或纳米材料-铁结合)的有效性。如果纳米材料能够发挥其抗菌特性，预计已知耐药性的细菌在用纳米材料和纳米材料-铁结合处理时，与抗生素相比，其MIC会更低。同时，纳米材料-铁的结合可能有助于将纳米材料输送到细菌，因为这些生物有几种机制帮助从细菌的外部环境吸收和移动铁，穿过细胞膜，进入细胞的内部区域，即周质。