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

生物和非生物材料都具有手性，这是一种被定义为“镜像”的属性，意味着存在具有特定方向的结构。这种特性在生命的基本组成部分中尤为突出，并在基本生物过程中发挥着关键作用。在合理设计新的仿生纳米材料以推进生物医学和改善人类健康方面，建立对生物环境中发生的相互作用中手性重要性的理解是至关重要的。这个CAREER项目将促进对手性纳米材料的理解，特别是在详细说明它们与组织和细胞等生物系统的相互作用方面。主要目标是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，以及它们在模型组织中的运动。本研究计划与教育目标相结合，旨在培养从幼儿园到研究生院的学生对科学，技术，工程和数学领域的兴趣和知识。这包括通过作为课后活动的一部分的“纳米生活”展览激发年轻学生的兴趣，通过在当地儿童博物馆的永久展览提高社区对纳米技术及其医学应用的接触，并在夏季为高中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培养一代未来的工程师。手性是生物和非生物形式物质的普遍属性。此属性控制材料在长度尺度上的组装和传输。生命的纳米级构件，包括蛋白质、核酸、聚糖和脂质，主要是手性的。因此，手性在关键的生物过程中具有非凡的意义。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CAREER项目的研究目标是精确设计手性纳米颗粒，用于系统和基础研究手性纳米颗粒与细胞膜和组织微环境中的脂质和蛋白质的相互作用。这项研究将寻求了解纳米颗粒的运输和吸收，并将采取跨学科的方法，结合模型膜系统的研究，细胞培养，计算模拟和肿瘤球体模型的评估。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。活动包括透过“纳米在生命中”展览，激发幼稚园至八年级学生对科学、科技、工程及数学的兴趣;透过在儿童博物馆举办的常设科学展览，向本地儿童介绍纳米科技及其在医学上的应用;以及为本地中学生及国际本科生提供暑期研究机会。总的来说，这个CAREER项目的长期目标是利用跨学科的方法合理设计仿生手性纳米粒子，以推进生物医学和改善人类健康，将这项研究与下一代工程师的教育和培训相结合，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准。

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.