CAREER: Engineering Chiral Nanoscale Interactions to Enhance Nanomaterial Transport and Uptake in Tissue and at Biointerfaces

职业：工程手性纳米级相互作用以增强组织和生物界面中纳米材料的运输和吸收

• 批准号: 2337387
• 负责人: Yichun Wang
• 金额: $ 54.93万
• 依托单位: University of Notre Dame
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-07-01 至 2029-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2337387&HistoricalAwards=false
• 关键词: CAREER; Engineering; Chiral; Nanoscale; Interactions

Both biological and nonbiological materials have chirality, a property defined as a “mirror image” and implying the presence of structures with a specific orientation. This property is particularly prominent in life's fundamental building blocks and plays a critical role in essential biological processes. In rationally designing new biomimetic nanoscale materials to advance biomedicine and improve human health, building an understanding of the importance of chirality in interactions that occur within biological environments is essential. This CAREER project will advance understanding of chiral nanomaterials, particularly in detailing their interactions with biological systems like tissues and cells. The primary objective is to develop and engineer nanomaterials and investigate their interactions and uptake within the membranes of living cells and their movement through model tissues. This research plan is integrated with educational goals, aiming to foster interest and knowledge in Science, Technology, Engineering, and Mathematics fields in students from kindergarten to graduate school. This includes stimulating interest in younger students through a "Nano in Life" exhibit as part of an after-school activity, enhancing community exposure to nanotechnology and its medical applications through a permanent exhibit at a local children's museum, and providing research opportunities for high school and international undergraduate students during the summer. This integrated educational approach is pivotal to the project, aiming to cultivate a generation of future engineers through exposure to nanotechnology. Chirality is a universal property of biological and nonbiological forms of matter. This property governs the assembly and transport of materials across length scales. The nanoscale building blocks of life, including proteins, nucleic acids, glycans, and lipids, are predominantly chiral. As such, chirality is of extraordinary significance in key biological processes. However, interactions of chiral nanomaterials in tissues and at biointerfaces remain poorly understood due to complexities of biological systems and challenges in rigorously engineering chiral nanomaterials. The research goal of this CAREER project is to precisely engineer chiral nanoparticles for a systematic and fundamental investigation of chiral nanoscale interactions with lipids and proteins of the cell membrane and in tissue microenvironments. This research will seek to understand nanoparticle transport and uptake and will take an interdisciplinary approach combining studies on model membrane systems, assessment in cell culture, computational simulations, and tumor spheroid models. The integrated education objectives of this CAREER project are designed to foster learning across all educational levels, from kindergarten to graduate school. Activities include stimulating interest of Science, Technology, Engineering and Mathematics among K-8 students through a “Nano in Life” exhibit, introducing nanotechnology and its medical applications to local children through a permanent science exhibit at a children’s museum, and offering summer research opportunities to local high school students and international undergraduate students. Overall, the long-term goal of this CAREER project is to use interdisciplinary approaches to rationally design biomimetic chiral nanoparticles to advance biomedicine and improve human health, integrating this research with the education and training of the next generation of engineers, and particularly women and underrepresented researchers.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.

生物和非生物材料都具有手性，这种特性被定义为“镜像”，意味着存在具有特定方向的结构，这种特性在生命的基本构建模块中尤为突出，并在合理的基本生物过程中发挥着关键作用。设计新的仿生纳米材料以推进生物医学和改善人类健康，了解手性在生物环境中发生的相互作用的重要性至关重要，该职业项目将促进对手性纳米材料的理解，特别是在手性纳米材料中。详细介绍它们与组织和细胞等生物系统的相互作用。该研究计划与教育目标相结合，旨在开发和设计纳米材料，并研究它们在活细胞膜内的相互作用和吸收。培养从幼儿园到研究生院学生对科学、技术、工程和数学领域的兴趣和知识，这包括通过作为课外活动一部分的“纳米生活”展览激发低年级学生的兴趣，增强社区对纳米技术的接触。纳米技术及其通过永久的医学应用在当地儿童博物馆展出，并在夏季为高中生和国际本科生提供研究机会，这种综合教育方法是该项目的关键，旨在通过接触纳米技术来培养一代未来的工程师。这种性质控制着生命的纳米级构建模块，包括蛋白质、核酸、聚糖和脂质，因此，手性具有非凡的性质。意义在于然而，由于生物系统的复杂性和严格设计手性纳米材料的挑战，手性纳米材料在组织和生物界面中的相互作用仍然知之甚少，该职业项目的研究目标是精确设计手性纳米粒子以实现系统性和基础性的研究。研究细胞膜和组织微环境中的脂质和蛋白质的手性纳米级相互作用。这项研究将寻求了解纳米颗粒的运输和摄取，并将采用跨学科方法，结合模型膜系统的研究、评估。该职业项目的综合教育目标旨在促进从幼儿园到研究生院的所有教育级别的学习，活动包括激发学生对科学、技术、工程和数学的兴趣。 -8名学生通过“生活中的纳米”展览，通过儿童博物馆的常设科学展览向当地儿童介绍纳米技术及其医学应用，并为当地高中生和国际本科生提供暑期研究机会。长期目标该职业项目的目的是利用跨学科方法合理设计仿生手性纳米粒子，以推进生物医学并改善人类健康，并将这项研究与下一代工程师，特别是女性和代表性不足的研究人员的教育和培训相结合。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。