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.

生物学和非生物学材料都具有手性，该特性被定义为“镜像”，并暗示存在具有特定方向的结构。该财产在生活的基本构建基础中尤为突出，并且在基本生物过程中起着至关重要的作用。在理性地设计新的仿生纳米级材料以促进生物医学并改善人类健康，建立对手性在生物环境中发生的相互作用中重要性的理解至关重要。这个职业项目将提高对手性纳米材料的了解，特别是在详细介绍其与组织和细胞等生物系统的相互作用时。主要目的是开发和设计纳米材料，并研究活细胞膜中的相互作用和吸收，及其通过模型组织的运动。该研究计划与教育目标融合在一起，旨在促进从幼儿园到研究生院的学生的科学，技术，工程和数学领域的兴趣和知识。这包括通过“人生中的纳米”展览激发对年轻学生的兴趣，作为课后活动的一部分，通过在当地儿童博物馆的永久性展览中增强了社区对纳米技术及其医疗应用的接触，并在夏季为高中和国际本科生提供了研究机会。这种综合的教育方法对该项目至关重要，旨在通过接触纳米技术来培养一代未来的工程师。手性是物质生物学和非生物学形式的普遍特性。该属性控制着长度尺度的材料的组装和运输。纳米级生命的基础，包括蛋白质，核酸，聚糖和脂质，主要是手性的。因此，手性在关键生物学过程中具有非凡的意义。然而，由于生物系统的复杂性以及严格的工程性手性纳米材料的复杂性，组织和生物界面中手性纳米材料的相互作用仍然很少理解。该职业项目的研究目标是精确地设计手性手性纳米颗粒，以进行手性纳米级相互作用与细胞膜和组织微环境中的脂质和蛋白质的系统性投资。这项研究将寻求了解纳米颗粒的运输和摄取，并采用跨学科的方法，结合了模型膜系统，评估，计算模拟和肿瘤球体模型的研究。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水平的学习。活动包括通过“生活中的纳米”展览刺激K-8学生中科学，技术，工程和数学的兴趣，通过在儿童博物馆的永久科学展览中将纳米技术及其医疗应用引入当地儿童，并向当地的高中生和国际学生提供夏季研究机会。总体而言，该职业项目的长期目标是使用跨学科的方法来理性设计仿生手性手性纳米颗粒，以提高生物医学并改善人类健康，将这项研究与下一代工程师的教育和培训相结合，尤其是女性，尤其是女性和培训，尤其是妇女和不足的研究人员，这些奖项反映了NSF的范围，这是NSF的众多范围，其成立了众多的依据，其含义的贵重宗教信仰是贵重的，这是贵重的，是贵重的，是贵重的，是贵重的，是贵重的，是熟悉的，是贵重的，是贵重的，是熟悉的，是贵重的，是熟悉的，是熟悉的，是熟悉的，是众所周知的，是众所周知。 标准。