Rational Design and Engineering of Graphene-Based Functional Nanocomposites as Effective Antimicrobial Reagents

抗药性细菌的增加和流行大大增加了治疗费用，更严重的是，增加了死亡率。因此，随着这些抗生素耐药性细菌的进化，用于治疗它们的药物也必须进化。在这个研究项目中，来自加州大学圣克鲁斯的Shaowei Chen教授提出使用基于氧化石墨烯和金属/金属氧化物纳米颗粒的复合材料作为下一代，低成本，有效的抗菌剂。这是为了利用它们在杀菌作用中的协同相互作用，其中复合物的抗微生物活性与单独组分的抗微生物活性相比显著增强。这项研究的成功将有助于为开发高性能抗菌试剂建立一个独特的平台。此外，拟议的研究将提供一个教育框架，在此框架内，学生研究人员将通过跨学科的努力获得许多复杂的技能。此外，部分研究活动将与针对少数民族，妇女和弱势本科生和合格高中生的几个外展计划紧密结合。学生将获得在传统课堂环境中无法获得的技能。在实验室研究中的实践经验和密集的培训预计将在他们未来的职业生涯中作为STEM劳动力的一部分灌输强烈的自信心和良好的职业道德。拟议研究的中心目标是促进我们对石墨烯的机械起源的理解-的纳米复合材料在抗菌应用，并制定了合理的设计和工程纳米复合材料的基本框架基于金属（氧化物）纳米颗粒和石墨烯衍生物作为低成本、高效率的抗微生物试剂。有三个具体任务：（a）石墨烯纳米片的设计和工程化，其中石墨烯结构（例如，尺寸、形态、表面官能化），并仔细检查对抗微生物活性的影响，（B）制备基于沉积在石墨烯纳米片上的金属（氧化物）纳米颗粒的功能性纳米复合材料，其中纳米复合材料的光反应性将被用作进一步操纵和优化抗微生物活性的有力变量，以及（c）通过结合（纳米）材料和分子生物学方法建立结构-活性相关性，重点在于阐明杀菌过程中的基本机制。拟议的研究是建立在陈教授实验室的最新进展基础上的，在该实验室中，过渡金属纳米颗粒和石墨烯量子点观察到了明显的抗菌活性，活性氧的产生被确定为主要的作用机制。在研究活动中将采用各种实验工具。对于材料表征，这些包括透射电子显微镜、X射线光电子能谱、X射线衍射、核磁共振、电子顺磁共振、UV-可见光、拉曼、红外和光致发光光谱。以大肠杆菌为例，通过紫外-可见光谱和荧光显微镜测量定量评估其抑制细菌生长的抗微生物活性，并通过RNA测序在活性氧生成和细菌细胞膜损伤的背景下检查其生物化学来源。一个直接，这两项工作之间的密切联系预计将揭示作用机制，并导致建立一个基本框架，在该框架内，石墨烯的合理设计和工程-该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查进行评估来支持的搜索.

The rise and prevalence of antibiotic-resistant bacteria have significantly increased the costs of treatment and, more seriously, death rates. Thus, it is imperative that as these antibiotic-resistant bacteria evolve, so must the medicines that are utilized to treat them. In this research project, Professor Shaowei Chen from the University of California Santa Cruz proposes to use composite materials based on graphene oxide and metal/metal oxide nanoparticles as next-generation, low-cost, potent antimicrobial reagents. This is to take advantage of their synergistic interactions in the bactericidal actions, where the antimicrobial activity of the composites is markedly enhanced as compared to those of the individual components. The success of the proposed research will help establish a unique platform for the development of high-performance antimicrobial reagents. Additionally, the proposed research will offer an educational framework within which student researchers will acquire many complex skills by undertaking an interdisciplinary effort. Also, part of the research activities will be closely integrated with several outreach programs targeting minority, women, and disadvantaged undergraduate students and qualified high-school students. The students will acquire skills that are unattainable in a conventional classroom setting. The hands-on experience and intense training in laboratory research are anticipated to instill a strong sense of self-confidence and good work ethics in their future careers as part of the STEM workforce.The central goal of the proposed research is to advance our understanding of the mechanistic origin of graphene-based nanocomposites in antimicrobial applications and to develop a fundamental framework for the rational design and engineering of nanocomposites based on metal (oxide) nanoparticles and graphene derivatives as low-cost, high-efficiency antimicrobial reagents. There are three specific tasks: (a) design and engineering of graphene nanosheets, where the graphene structures (e.g., size, morphology, surface functionalization) will be systematically manipulated and the impacts on the antimicrobial activity will be carefully examined, (b) preparation of functional nanocomposites based on metal (oxide) nanoparticles deposited on graphene nanosheets, where the nanocomposite photo reactivity will be exploited as a powerful variable in the further manipulation and optimization of the antimicrobial activity, and (c) establishment of a structure-activity correlation by combining (nano)materials and molecular biology approaches, with a focus on unravelling the fundamental mechanisms in the bactericidal process. The proposed research is built upon recent progress in Professor Chen's laboratory where apparent antimicrobial activity was observed with transition-metal nanoparticles as well as graphene quantum dots, with the production of reactive oxygen species identified as the leading mechanism of action. A wide range of experimental tools will be employed in the research activities. For materials characterizations, these include transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, nuclear magnetic resonance, electron paramagnetic resonance, UV-visible, Raman, infrared, and photoluminescence spectroscopy. Using Escherichia coli as the illustrating example, the antimicrobial activity towards the inhibition of bacterial growth will be quantitatively assessed by UV-visible spectroscopic and fluorescence microscopic measurements, and the biochemical origins will be examined by RNA sequencing, within the context of reactive oxygen species generation and bacteria cell membrane damages. A direct, intimate correlation between these two efforts is anticipated to shed light on the mechanisms of action and lead to the establishment of a fundamental framework within which rational design and engineering of graphene-based nanocomposites can be achieved for optimal antimicrobial performance.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.