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

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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.