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.

纳米尺度的相互作用决定了纳米粒子在环境、生物和医学应用中的安全性和有效性。为了更好地开发纳米颗粒在这些应用中的潜力，需要对纳米尺度的相互作用有一个基本的了解。该项目将通过使用独特的生物分析方法系统地研究纳米颗粒之间的相互作用、纳米颗粒-细胞相互作用和纳米颗粒在细胞内的运输，从而提供对单个颗粒和单细胞水平上的纳米尺度相互作用的定量理解。该项目的潜在科学影响将是为设计更安全、更有效的纳米颗粒提供工程指导方针，通过对纳米尺度相互作用的更深入的定量理解，从而更好地控制。教育的核心影响基于美国原住民和俄克拉何马州西南部农村地区其他未得到充分服务的高三学生通过全年研究整合教育和推广活动来参与生物技术，以激励他们在科学和工程领域取得成功。在环境、生物和医疗应用中安全有效地使用纳米颗粒需要更好地定量了解纳米颗粒与生物介质和系统的相互作用。该项目将建立一个新的研究范式，通过三个研究目标，基于独特的无标记和原位定量生物分析方法，在单粒子和单细胞水平上系统地研究纳米级相互作用的机制和动力学。在目标1中，纳米粒子之间的相互作用将被量化。目标2将评估纳米颗粒与细胞之间的相互作用。目标3将以独特的时空分辨率确定纳米颗粒在细胞内的传输。这些定量的和机械的研究有可能为纳米颗粒的工程提供信息，这些纳米颗粒可以有效地克服生物障碍，实现安全和有效的生物和医疗应用。这项研究还将使人们能够更好地从定量和机理上了解纳米粒子与环境的相互作用和相关的生态效应。这一科学愿景将与美国原住民和其他未得到充分服务的高三学生通过一项名为俄克拉荷马州美洲原住民生物技术参与(BE4NANO)的独特计划相结合。与当地美洲原住民部落、公立高中、技术中心和大学盟友合作，将有两个主要教育目标：(I)通过全年活动让这些学生参与生物科技，以及(Ii)在学校内为这些学生创建学术和社会支持网络。通过BE4NANO，高中生将受到启发，考虑成为科学家和工程师。此外，PI将提供支持和鼓励，以最大限度地取得成功，从而增加大学科学、技术、工程和数学专业的美国原住民学生数量，并将这些学生保留在他们的学习计划中。该项目由化学、生物工程、环境和运输系统(CBET)分部内的纳米尺度互动计划和既定的激励竞争研究计划(EPSCoR)共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

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

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.

用肝素多糖控制先天免疫细胞中的纳米颗粒摄取。

• 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

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

Quantifying Intracellular Nanoparticle Distributions with Three-Dimensional Super-Resolution Microscopy.

• DOI: 10.1021/acsnano.2c12808
• 发表时间: 2023-05-09
• 期刊: ACS NANO
• 影响因子: 17.1
• 作者: Sheth, Vinit;Chen, Xuxin;Mettenbrink, Evan M.;Yang, Wen;Jones, Meredith A.;M'Saad, Ons;Thomas, Abigail G.;Newport, Rylee S.;Francek, Emmy;Wang, Lin;Frickenstein, Alex N.;Donahue, Nathan D.;Holden, Alyssa;Mjema, Nathan F.;Green, Dixy E.;DeAngelis, Paul L.;Bewersdorf, Joerg;Wilhelm, Stefan
• 通讯作者: Wilhelm, Stefan