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

从我的学位和额外的工作中获得的知识，我希望对有可能作为纳米抗生素的物质的产生和应用进行研究。纳米材料，如银（Ag），由于其抗菌特性，已经被用于伤口敷料和可重复使用购物袋的衬里，而纳米材料通常被认为使用不同的机制来造成细菌死亡。银只是已知具有这些特性的一种纳米材料，尽管其他纳米材料，如铜、氧化锌、钛和二氧化硅，也被认为具有这种可开发的特性。也有人提出，与其他也被认为是未来抗菌替代品的新疗法相比，纳米材料的使用可能具有较低的毒性水平。考虑到这一点，纳米材料的临床应用可能比其他可能具有更严重的脱靶毒性的物质更有利。纳米材料所具有的抗菌特性使其成为临床（和潜在的环境）抗生素使用的有吸引力的替代品。我的目的是比较标准抗生素与纳米材料（那些先前被描述为抗菌的）和与铁（Fe）共轭的纳米材料的抗菌活性和趋势。铁是一种必需的微量元素，细菌需要铁才能致病，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向细菌的传递，同时可能增强抗菌效果。该项目的概念侧重于使用纳米材料-铁偶联物来靶向目前被认为对人类最有问题的细菌；那些已知有几种抗生素耐药性的人。对于一种最终用于临床的新疗法，了解哪些物质可能对人体系统产生的影响是很重要的。该项目旨在考虑到这一点，将哺乳动物细胞纳入实验。这是至关重要的，以便深入了解与毒性相关的潜在副作用，提供有意义的结论，这些结论在生理学上是相关的，并将用于未来的临床应用。此外，通过使用细胞系，如Caco-2细胞，这将减少研究中对动物的需求，这可能是浪费和不道德的，除了不需要内政部的批准，这将需要使用动物和原代细胞实验。通过研究最低抑制浓度（MIC）（阻止细菌生长所需物质的最低浓度），可以指示每种治疗条件（抗生素，单独使用纳米材料或纳米材料-铁偶联）的效果。如果纳米材料能够发挥其抗菌性能，那么可以预期，与抗生素相比，使用纳米材料和纳米材料-铁偶联处理具有已知抗性的细菌将具有更低的MIC。同时，纳米材料-铁结合可能有助于纳米材料向细菌的传递，因为这些生物有几种机制来帮助铁从细菌的外部环境中吸收和移动，穿过细胞包膜，进入细胞的内部区域，即周质。

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.