CAREER: Understanding Nanoscale Interactions at Single-Particle and Single-Cell Levels

职业：了解单粒子和单细胞水平的纳米级相互作用

• 批准号: 2048130
• 负责人: Stefan Wilhelm
• 金额: $ 76.17万
• 依托单位: University of Oklahoma Norman Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2048130&HistoricalAwards=false
• 关键词: CAREER; Understanding; Nanoscale; Interactions; Single

Nanoscale interactions determine nanoparticle safety and effectiveness in environmental, biological, and medical applications. To better exploit the potential of nanoparticles for these applications, a fundamental understanding of nanoscale interactions is required. This project will provide a quantitative understanding of nanoscale interactions at single particle and single cell levels by systematically studying inter-nanoparticle interactions, nanoparticle-cell interactions, and nanoparticle intracellular transport using unique bio-analytical methods. The potential scientific impact of this project will be in providing engineering guidelines for the design of safer and more effective nanoparticles made possible by a deeper quantitative understanding, and thus better control, of nanoscale interactions. Core educational impacts are based on bionanotechnology engagement of Native American and other underserved high school juniors in rural Southwest Oklahoma via year-round research-integrated education and outreach activities to inspire successful careers in science and engineering.The safe and effective use of nanoparticles in environmental, biological, and medical applications requires a better quantitative understanding of nanoparticle interactions with biological media and systems. This project will establish a new research paradigm to systematically study the mechanisms and kinetics of nanoscale interactions based on unique label-free and in situ quantitative bio-analytical methods at single particle and single cell levels via three research objectives. In Objective 1, inter-nanoparticle interactions will be quantified. Nanoparticle-cell interactions will be assessed in Objective 2. In Objective 3, nanoparticle intracellular transport will be determined with unique spatiotemporal resolution. These quantitative and mechanistic studies have the potential to inform the engineering of nanoparticles that efficiently overcome biological barriers for safe and effective biological and medical applications. This research will additionally enable a better quantitative and mechanistic understanding of nanoparticle environmental interactions and associated ecological effects. The scientific vision will be integrated with the engagement of Native American and other underserved high school juniors in bionanotechnology via a unique program termed Bionanotechnology Engagement for Native Americans in Oklahoma (BE4NANO). In partnership with local Native American tribes, public high schools, a technology center, and university allies, there will be two primary educational objectives to (i) engage these students in bionanotechnology via year-round activities, and to (ii) create academic and social support networks for these students within the institution. Through BE4NANO, high school students will be inspired to consider careers as scientists and engineers. In addition, the PI will provide support and encouragement to maximize success, thereby increasing the number of Native American students in college science, technology, engineering, and mathematics programs and retaining these students in their programs of study. Students will be empowered to engage and inspire the next generation of BE4NANO participants within their underserved communities, creating a positive and inclusive feedback loop to sustain this holistic research-integrated education and outreach program.This project is jointly funded by the Nanoscale Interactions Program within the Chemical, Bioengineering, Environmental and Transport Systems (CBET) Division and the Established Program to Stimulate Competitive Research (EPSCoR).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.

纳米级相互作用决定了纳米颗粒的安全性和在环境，生物学和医疗应用中的有效性。为了更好地利用纳米颗粒的潜力，需要对纳米级相互作用有基本的了解。该项目将通过系统地研究纳米颗粒相互作用，纳米颗粒 - 细胞相互作用以及使用独特的生物分析方法的纳米颗粒相互作用，对单个粒子和单细胞水平的纳米级相互作用进行定量理解。该项目的潜在科学影响将在为设计指南提供更安全和更有效的纳米颗粒的设计，这是通过更深入的定量理解，从而更好地控制纳米级相互作用的。核心教育影响是基于美洲原住民和其他服务不足的高中大三学生在俄克拉荷马州农村地区通过全年研究的研究综合教育和外展活动的参与，以激发科学和工程的成功职业。 ，生物学和医疗应用需要对纳米颗粒与生物学媒体和系统的相互作用进行更好的定量了解。该项目将建立一个新的研究范式，以系统地研究基于独特的无标签和原位定量生物分析方法在单个粒子和单个细胞水平上，通过三个研究目标研究纳米级相互作用的机制和动力学。在目标1中，将量化纳米颗粒相互作用。纳米颗粒 - 细胞相互作用将在目标2中评估。在目标3中，纳米颗粒内运输将通过独特的时空分辨率确定。这些定量和机械研究有可能为有效克服生物障碍的纳米颗粒的工程提供信息，以实现安全有效的生物学和医疗应用。这项研究还将对纳米颗粒环境相互作用和相关的生态影响有更好的定量和机械理解。科学愿景将与美洲原住民和其他服务不足的高中大三学生在Bionanotechnology中的参与融合，这是一项独特的计划，称为俄克拉荷马州原住民的Bionanotechnology参与（BE4NANO）。与当地的美国原住民部落，公立高中，技术中心和大学盟友合作，将有两个主要的教育目标，以（i）通过全年活动与这些学生一起参与Bionanotechnology，以及（ii）创建学术和学术和这些学生的社会支持网络。通过BE4NANO，将启发高中生将职业视为科学家和工程师。此外，PI将提供支持和鼓励，以最大程度地提高成功，从而增加美国原住民学生在大学科学，技术，工程和数学计划中的数量，并将这些学生留在其学习计划中。学生将有能力参与和激发其服务不足的社区中的下一代BE4NANO参与者，创建一个积极而包容的反馈循环，以维持这一整体研究综合的教育和外展计划。该项目由纳米级互动计划共同资助。化学，生物工程，环境和运输系统（CBET）部门以及启发竞争研究的既定计划（EPSCOR）。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛影响的评估来审查标准的评估值得的支持。

项目成果

Quantifying Chemical Composition and Reaction Kinetics of Individual Colloidally Dispersed Nanoparticles

• DOI: 10.1021/acs.nanolett.1c03752
• 发表时间: 2021-12-28
• 期刊: NANO LETTERS
• 影响因子: 10.8
• 作者: Donahue, Nathan D.;Kanapilly, Sandy;Wilhelm, Stefan
• 通讯作者: Wilhelm, Stefan

Controlling Nanoparticle Uptake in Innate Immune Cells with Heparosan Polysaccharides.

• DOI: 10.1021/acs.nanolett.2c02226
• 发表时间: 2022-09-14
• 期刊: NANO LETTERS
• 影响因子: 10.8
• 作者: Yang, Wen;Frickenstein, Alex N.;Sheth, Vinit;Holden, Alyssa;Mettenbrink, Evan M.;Wang, Lin;Woodward, Alexis A.;Joo, Bryan S.;Butterfield, Sarah K.;Donahue, Nathan D.;Green, Dixy E.;Thomas, Abigail G.;Harcourt, Tekena;Young, Hamilton;Tang, Mulan;Malik, Zain A.;Harrison, Roger G.;Mukherjee, Priyabrata;DeAngelis, Paul L.;Wilhelm, Stefan
• 通讯作者: Wilhelm, Stefan

Disabling partners in crime: Gold nanoparticles disrupt multicellular communications within the tumor microenvironment to inhibit ovarian tumor aggressiveness.

• DOI: 10.1016/j.mattod.2022.01.025
• 发表时间: 2022-06
• 期刊: MATERIALS TODAY
• 影响因子: 24.2
• 作者: Zhang, Yushan;Elechalawar, Chandra Kumar;Yang, Wen;Frickenstein, Alex N.;Asfa, Sima;Fung, Kar-Ming;Murphy, Brennah N.;Dwivedi, Shailendra K.;Rao, Geeta;Dey, Anindya;Wilhelm, Stefan;Bhattacharya, Resham;Mukherjee, Priyabrata
• 通讯作者: Mukherjee, Priyabrata

Bioimaging with Upconversion Nanoparticles

• DOI: 10.1002/adpr.202200098
• 发表时间: 2022-12-01
• 期刊: ADVANCED PHOTONICS RESEARCH
• 作者: Mettenbrink, Evan M.;Yang, Wen;Wilhelm, Stefan
• 通讯作者: Wilhelm, Stefan

Nanoparticle Surface Engineering with Heparosan Polysaccharide Reduces Serum Protein Adsorption and Enhances Cellular Uptake.

• DOI: 10.1021/acs.nanolett.2c00349
• 发表时间: 2022-03-09
• 期刊: NANO LETTERS
• 影响因子: 10.8
• 作者: Yang, Wen;Wang, Lin;Fang, Mulin;Sheth, Vinit;Zhang, Yushan;Holden, Alyssa M.;Donahue, Nathan D.;Green, Dixy E.;Frickenstein, Alex N.;Mettenbrink, Evan M.;Schwemley, Tyler A.;Francek, Emmy R.;Haddad, Majood;Hossen, Md Nazir;Mukherjee, Shirsha;Wu, Si;DeAngelis, Paul L.;Wilhelm, Stefan
• 通讯作者: Wilhelm, Stefan