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

摘要：20世纪90年代以来，抗生素耐药菌引起的传染病在全球范围内呈上升趋势，已成为严重的传染病威胁。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以及在各种其他环境中广泛使用消毒剂作出反应的结果。值得注意的是，新的耐药机制的出现和全球传播速度与新药的开发速度一样快，这对传统抗生素/抗微生物药物领域构成了严重挑战，但也促使全球寻找替代抗微生物策略。在对抗耐药性的许多策略中，开发与传统抗生素在机制上不同的抗菌剂是一种更有效的选择。具体来说，在本项目探索的技术上，碳点被开发为一类新的抗菌剂，通过在可见光/自然光下产生的活性物质杀死细菌细胞。该项目由美国国家科学基金会材料研究部生物材料计划资助，重点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，目标是建立一种有效的替代抗菌技术来对抗耐药细菌。该项目还将对促进知识驱动型经济新技术的开发和转让以及食品、水安全和国防、教育和人力资源开发等其他领域产生重大而广泛的影响。由于超过85%的学生来自代表性不足的少数群体，拟议的多学科研究预计将以各种方式为这些本科生提供良好的研究培训环境，包括直接参与研究，学生交换计划（在合作者的实验室之间）和夏季研讨会。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激活杀微生物功能。碳纳米点可以被认为是一种特殊的“核-壳”纳米结构，每个碳纳米粒子都有一个小的碳纳米粒子核和一个薄的软材料壳。它们在整个可见光谱上都具有很强的吸收性，它们的光激发态特性和氧化还原过程类似于半导体量子点中典型的特性，但具有独特的优势。跨学科项目团队将开发和验证CDots作为一种新的可见光/自然光激活的杀微生物剂，用于对抗多种耐药细菌，选择的测试物种包括从农场动物中分离的肠沙门氏菌、单核细胞增殖性李斯特菌、空肠弯曲杆菌和大肠弯曲杆菌。本项目的科学目标是：(1)系统评价CDots对耐药菌的抑菌作用与CDots表面电荷、大小、合成方法等几个主要因素的关系；(2)阐明和理解CDots抗菌功能的机理，重点研究CDots的结构和光化学参数与抗菌性能的相关性；(3)探索不同构型的碳/TiO2杂化点对耐药微生物和病毒的抗菌性能。该项目的智力优势包括生物材料抗菌应用领域的进步和CDots光激活抗菌功能的建立，以对抗日益严重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、水安全和国防方面找到应用。该项目的广泛影响包括为参与两所合作机构材料科学和生物应用交叉领域的学生，特别是来自代表性不足群体的本科生和K-12学生提供优秀的研究培训机会。

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.