Collaborative Research: Microbicidal Carbon Dots for Combating Anti-Biotic Resistance and Beyond

非技术摘要：自20世纪90年代以来，由抗生素耐药细菌引起的传染病在全球范围内呈上升趋势，并成为这些疾病的严重威胁。抗生素耐药性主要是细菌对人类或农业中过度使用抗生素的反应，以及在各种其他环境中广泛使用消毒剂的结果。值得注意的是，新的耐药机制出现并在全球传播的速度与新药开发的速度一样快，这对传统抗生素/抗菌剂领域提出了严重挑战，但也促使全球寻找替代抗菌策略。在对抗耐药性的许多策略中，开发与传统抗生素机械上不同的抗菌剂是一个更有效的选择。具体地说，在本项目探索的技术基础上，碳点被开发为一类新的抗菌剂，它通过在可见光/自然光下产生的活性物种杀死细菌细胞。该项目由国家科学基金会材料研究部内的生物材料计划资助，重点是评估和验证碳点杀灭耐药细菌的潜力，并了解相关的工作机制，目的是建立一种有效的替代抗菌技术来对抗耐药细菌。该项目还将在刺激新技术的开发和转让方面产生重大的更广泛的影响，以促进知识驱动的经济，以及在食品、水安全和国防、教育和人力资源开发等其他领域的应用。由于85%以上的学生来自少数族裔群体，拟议的多学科研究预计将通过各种方式为这些本科生提供一个很好的研究培训环境，包括直接参与研究、学生交流计划(合作者实验室之间)和暑期研讨会。技术摘要：本合作研究项目旨在探索新开发的碳点(CDots)对耐药细菌病原体的光活化杀菌功能。CDot可以被认为是一种特殊的核壳纳米结构，每种结构都有一个小的碳纳米颗粒核心和一个由软材料组成的薄壳。它们在整个可见光谱范围内都有很强的吸收，它们的光激发态性质和氧化还原过程类似于半导体量子点中常见的那些，但有独特的优势。跨学科项目团队将开发和验证CDots作为一种新型的可见光/自然光激活的杀微生物剂，以对抗多重耐药细菌，所选物种包括从农场动物分离的肠沙门氏菌、单核细胞增生性李斯特菌、空肠弯曲菌和结肠弯曲菌。该项目的科学目标是：(1)从CDOT表面电荷、大小和合成方法等几个主要因素出发，系统评价CDot对耐药细菌的抗菌功能；(2)从机理上阐明和了解CDot的抗菌功能，重点关注CDot的结构和光化学参数与所观察到的杀菌性能的相关性；以及(3)探索不同构型的碳/二氧化钛杂化点，以增强对耐药微生物和病毒的抗菌性能。该项目的学术价值包括推进了用于抗菌应用的生物材料领域，并建立了CDots的光激活抗菌功能，以对抗日益增长的抗生素耐药性威胁。除了解决国家医疗保健中的关键问题外，这些材料还可以在食品、水安全和国防方面得到应用。该项目的广泛影响包括在两个合作机构为参与材料科学和生物学应用的跨学科领域的学生提供极好的研究培训机会，特别是为来自代表性不足群体的本科生和K-12学生。

Non-Technical Abstract: Since the 1990s, infectious diseases caused by antibiotic-resistant bacteria have been increasing globally and becoming a serious threat from these diseases. Antibiotic resistance is mostly a consequence of bacterial response to excessive uses of antibiotics in humans or agriculture and the widespread usage of disinfectants in a variety of other settings. Noticeably, new resistance mechanisms emerge and spread globally as fast as new drugs being developed, which has posted serious challenges to the realm of traditional antibiotics/antimicrobial agents, but has also motivated a global search for alternative antimicrobial strategies. Among the many strategies that have been pursued in combating the resistance, the development of antibacterial agents that are mechanistically different from traditional antibiotics is a more effective option. Specifically, on the technology explored in this project, carbon dots are developed as a new class of antimicrobial agents which kill bacterial cells through reactive species generated under visible/natural light. This project, funded by the Biomaterials Program within the National Science Foundation's Division of Materials Research, focuses on the evaluation and validation of the potential of carbon dots for killing drug-resistant bacteria and developing an understanding of related working mechanisms, with the goal of establishing an effective alternative antimicrobial technology for combating drug-resistant bacteria. This project will also have significant broader impacts in stimulating the development and transfer of new technologies for the knowledge-driven economy, and other areas such as applications in food, water safety and national defense, education and human resource development. With more than 85% of the student population from underrepresented minority groups, the proposed multidisciplinary research is expected in providing a great research training environment for these undergraduate students in a variety of ways, including direct participation in research, student exchange programs (between the collaborators' labs), and summer workshops. Technical Abstract: This Collaborative Research project is to explore the light-activated microbicidal functions of newly developed carbon dots (CDots) against drug-resistant bacterial pathogens. CDots may be considered as a special kind of "core-shell" nanostructures, each with a small carbon nanoparticle core and a thin shell of soft materials. They are strongly absorptive over the entire visible spectrum, and their photoexcited state properties and redox processes resemble those typically found in semiconductor quantum dots, but with unique advantages. The interdisciplinary project team will develop and validate CDots as a new class of visible/natural light-activated microbicidal agents against multi-drug resistant bacteria, with the selected species for testing including Salmonella enterica, Listeria monocytogenes, and Campylobacter jejuni and Campylobacter coli isolated from farm animals. The scientific objectives of the project are: (1) systematic evaluation of CDots' antibacterial function to the drug-resistant bacteria in relation to several major factors including Cdot surface charge, size, and synthesis approach; (2) mechanistic elucidation and understanding of CDots' antimicrobial function, focusing on correlations of the structural and photochemical parameters of CDots with the observed bacteria-killing performances; and (3) exploration of Carbon/TiO2 hybrid dots of different configurations for enhanced antimicrobial performance against drug-resistant microbes and viruses. The intellectual merits of the project include the advancement of the biomaterial field for antimicrobial applications and the establishment of the photo-activated antimicrobial functions of CDots for combating the increasing threat of antibiotic resistance. In addition to addressing the critical issues in national healthcare, these materials could find applications in food, water safety and national defense. The broad impacts of the project include providing excellent research-for-training opportunities for participating students in the interdisciplinary field at the interface of material science and biological applications at the two collaborating institutions, especially for undergraduate and K-12 students from underrepresented groups.