Collaborative Research: Using Anisotropic Surface Coating of Nanoparticles to Tune Their Antimicrobial Activity

合作研究：利用纳米颗粒的各向异性表面涂层来调节其抗菌活性

• 批准号: 2313754
• 负责人: Ying Li
• 金额: $ 20.14万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2313754&HistoricalAwards=false
• 关键词: Collaborative; Research; Using; Anisotropic; Surface

The rapid rise in antimicrobial/antibiotic resistance in pathogenic bacteria is a global public health threat. Antimicrobial resistance occurs when bacteria and fungi evolve to stop responding to antibiotics and to continue to grow. Each year in the US alone, antimicrobial-resistant bacteria or fungi cause infection in more than 2.8 million people and more than 35,000 deaths. Developing alternatives to traditional antibiotics is critical for addressing this global challenge. This collaborative project supports fundamental research to develop a new type of antimicrobial nanoparticle to combat antibiotic-resistant bacteria. These nanoparticles are unique in that they display a non-uniform coating of hydrophobic and positively charged molecules. Such nanoparticles are expected to act through novel antibiotic mechanisms that are less likely to cause acquired drug resistance in bacteria. The research team will combine experiments with computational modeling to elucidate how interactions of these nanoparticles with bacteria depend on the non-uniform surface chemistry of nanoparticles and the cell wall chemistry of bacteria. The mechanistic understanding from this study will guide the rational design of antimicrobial nanoparticles against a wide range of pathogenic bacteria. By integrating nanoscience research with educational and outreach activities this collaborative project outlines interdisciplinary approaches to promote critical thinking and increase diversity in STEM. These approaches include the development of introductory undergraduate courses that integrate science teaching with art, a collaborative outreach project to K-12 students in rural areas, and training of the next generation of researchers, especially underrepresented minority groups. Developing broad-spectrum antimicrobial nanoparticles is challenging because a single nanoparticle design cannot be a one-size-fits-all solution effective against all bacteria. Instead, nanoparticles whose antimicrobial activity can be tuned to match the bacterial diversity are needed. This collaborative project is focused on developing a new strategy to tune nanoparticle-bacteria interactions by using the anisotropic organization of ligands on nanoparticles. Specifically, experiments will be combined with molecular dynamics simulations to investigate interactions of amphiphilic nanoparticles with model bacterial membranes and a diverse selection of Gram-negative bacterial strains, many of which are resistant to most available antibiotics. The expected results will establish the structure-activity relationship governing the antimicrobial mechanisms of the amphiphilic nanoparticles. Such new understanding will enable the development and optimization of antimicrobial nanoparticles that are potentially more potent than existing ones and whose effects are tunable. The educational and outreach goal of this project is to develop interdisciplinary approaches to promote critical thinking and increase diversity in STEM. These approaches include innovation of introductory undergraduate courses by integrating art with science teaching, a collaborative outreach project to K-12 students in rural areas, and training of next generation of researchers with a particular emphasis on the involvement of underrepresented minority groups.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.

致病细菌中抗菌/抗生素抗性的迅速增加是全球公共卫生威胁。当细菌和真菌进化以停止对抗生素反应并继续生长时，就会发生抗菌耐药性。仅在美国，抗菌细菌或真菌就会每年在280万人和35,000多人的死亡中引起感染。开发传统抗生素的替代方案对于应对这一全球挑战至关重要。该协作项目支持基本研究，以开发一种新型的抗菌纳米颗粒来对抗抗抗生素的细菌。这些纳米颗粒的独特之处在于它们显示出疏水和带正电分子的不均匀涂层。这种纳米颗粒有望通过新型的抗生素机制作用，这些抗生素机制不太可能引起细菌中获得的耐药性。研究团队将将实验与计算建模相结合，以阐明这些纳米颗粒与细菌的相互作用如何依赖于纳米颗粒的不均匀表面化学和细菌的细胞壁化学。这项研究的机械理解将指导抗菌纳米颗粒的合理设计对广泛的致病细菌。通过将纳米科学研究与教育和外展活动相结合，该协作项目概述了跨学科的方法，以促进批判性思维并增加STEM的多样性。这些方法包括开发介绍性的本科课程，这些课程将科学教学与艺术联系起来，为农村地区的K-12学生进行协作外展项目，以及对下一代研究人员的培训，尤其是代表性不足的少数群体。开发大光​​谱抗菌纳米颗粒是具有挑战性的，因为单个纳米颗粒的设计不能是对所有细菌有效的单一适合溶液。取而代之的是，可以调节抗菌活性以匹配细菌多样性的纳米颗粒。该协作项目的重点是制定一种新的策略来通过在纳米颗粒上使用配体的各向异性组织来调整纳米粒子 - 细菌相互作用。具体而言，实验将与分子动力学模拟结合使用，以研究两亲性纳米颗粒与模型细菌膜的相互作用，并选择了革兰氏阴性菌株的多样化选择，其中许多菌株对大多数可用的抗生素具有抗性。预期的结果将建立统治两亲性纳米颗粒的抗菌机制的结构活性关系。这种新的理解将使抗菌纳米颗粒的开发和优化可能比现有纳米颗粒更有效，并且其效果可调。该项目的教育和外展目标是开发跨学科的方法来促进批判性思维并增加STEM的多样性。这些方法包括通过将艺术与科学教学结合，为农村地区的K-12学生进行协作外展项目的创新，以及对下一代研究人员的培训，并特别强调专门针对不足的少数民族群体的参与。这一奖项反映了NSF的法定任务和审查的范围，这表明了审查的范围。