EAGER-Harnessing natural killer cell-derived extracellular vesicles as anti-viral nanomaterials

NON-TECHNICAL ABSTRACT:

Natural killer cell-derived extracellular vesicles (NKE) are natural nanoparticles that are inherently biocompatible, stable in vivo, and contain anti-viral components. As such, investigating the materials properties of NKE will be critical to informing the design of synthetic, biomimetic nanoparticles that can be scaled-up for anti-viral application including COVID-19. To meet these needs, the overall goal of this EAGER award by the Biomaterials Program is to study the nanomaterial properties, membrane composition, and cargo of NKE. Using this new knowledge, the PI and her lab will test how these material properties affect membrane fusion, as well as cell internalization and anti-viral function against SARS-CoV-2 infection. Since NK cell activity has been found to differ among various patient populations, the PI will also elucidate how the materials properties of extracellular vesicles vary with biological factors, and can be used to obtain new knowledge that is critical for compatibility, stability, and overall performance of drug delivery systems. These research efforts will be integrated with education and outreach initiatives for K-12, undergraduate, and graduate students and for the public. The activities at the college and graduate levels are centered on recruitment, mentorship, and training women, URM, and LGBTQ students through in-depth research experiences, while K-12 activities are based on classroom lectures and hands-on demos. In addition, the PI will interact with the public through an established collaboration with the California Science Center and a social media platform for K-12 students. The goal is to inspire, engage, and prepare the next generation of scientists and engineers from diverse backgrounds to develop innovative solutions that can benefit global public health.

TECHNICAL ABSTRACT:

Natural killer (NK) cells are the first line of defense against viral infections and helps eliminate unhealthy host cells. Although NK cells have been proposed as a cell-based therapy against diseases caused by viral infections such as COVID-19, cell therapy has challenges including limited cell survival in vivo, short shelf-life, and high cost. Instead, the cytotoxic, extracellular vesicles (EVs) that endow natural killing properties to NK cells have the potential to be scaled-up as long-term, off-the-shelf drug delivery carriers and can be used to inform the design of stable, biomimetic drug delivery carriers for anti-viral application. To that end, the PI and her lab will first 1) characterize the material properties, as well as lipid, protein, and RNA membrane and cargo composition of NK EVs (NKE) originating from several human sources. Then, the PI and her lab will 2) evaluate NKE cell internalization and anti-viral activity in cells infected with SARS-CoV-2 and assess how differences in NKE composition and materials properties influences their function. Success of the research plan is anticipated to advance fundamental knowledge of NKE, and elucidate their material properties as it relates to anti-viral function. Thus, the results from the research proposal may be significant during the current pandemic (e.g. COVID-19) in evaluating NKE as a novel source of anti-viral therapy, but will have potential benefits for immunotherapy in other viral infections. The research plan is integrated with the education and outreach plan which includes: 1) recruitment, training, and mentoring of undergraduate and graduate students from diverse backgrounds including women, URM, and LGBTQ groups through in-depth research experiences, 2) classroom lecture and hands-on activities regarding bio-nanomaterials including nanoparticle carriers in recent COVID-19 vaccines (32nd Street School, Los Angeles Unified School District), and 3) NanoDays, an annual program that will include bio-nanotechnology demos at the California Science Center, and NanoPeek, our social media platform that showcases bio-nanotechnology content. Together, these initiatives aim to excite, engage, and disseminate knowledge to a diverse audience ranging from K-12 to the public regarding bionanomaterials in medicine and its potential to solve global public health issues such as pandemics. The effectiveness of the programs will be evaluated for each activity.

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.