Nano-directed therapeutics for neonatal brain injury

For the treatment of brain diseases, therapeutic penetration and cellular interaction within the brain is critical to the success of the therapeutic. Nanotechnology, which consists of small, highly-tailorable platforms, can provide a modality to survey a disease environment, as well as a vehicle for site-specific, controlled, and sustained-release of therapeutics to the central nervous system (CNS). Our research combines nanotechnology, data science, imaging, and neuroscience tools with preclinical models to understand and overcome drug delivery limitations in the brain. We focus on drugs that can affect multiple pathways and have a solubility and/or delivery problem - that is, the drug is either not soluble in aqueous solutions or it is not able to reach its target site in high enough concentrations to be effective. To improve delivery, we use therapeutic nanoparticle platforms that are polymer-based, incorporate materials that are approved for human use, and have been tested extensively in adult populations but not in children or newborns. In this talk, we demonstrate the importance of using multiple platforms to evaluate nanotherapeutic behavior, effect, and fate in the brain. Our ex vivo cultures include stimuli that replicate aspects of in vivo injury conditions, such as oxygen-glucose deprivation, glutamate toxicity, or exposure to lipopolysaccharide (LPS). In vitro and ex vivo, we test for toxicity and dose response; ex vivo, we evaluate regionally dependent cellular uptake and downstream mechanistic effects of the nanotherapeutic platform; in vivo, we quantify biodistribution and measure improvements in gross injury and neuropathology in response to treatment. We show that we can engineer more effective therapeutics for neuroprotection in neonatal and pediatric populations, which are vastly underserved by technology development.

Dr Elizabeth Nance

Dr. Elizabeth Nance is the Clare Boothe Luce Assistant Professor of Chemical Engineering at the University of Washington (UW, Seattle Washington), with an appointment in Radiology and affiliations with the UW Center on Human Development and Disability and eScience Institute.  Elizabeth received her Ph.D. from Johns Hopkins University in Chemical & Biomolecular Engineering and completed a postdoc in Anesthesiology and Critical Care Medicine, with a research emphasis in neuroscience, at Johns Hopkins School of Medicine. Her research develops methods to understand the developing brain’s response to injury or disease, and engineer nanotherapeutic platforms to treat brain disease. She developed the first brain-penetrating particle platform and was a contributing team member to the first nanoparticle to reach clinical trials for kids with non-cancerous brain disease. In 2019, she received the Presidential Early Career Achievement in Science & Engineering award, the “highest honor bestowed by the U.S. government on outstanding scientists and engineers.” She has been recognized as the European Union Horizons 2020 Inspiring Young Scientist in Nanomedicine, a Young Innovator in Nanobiotechnology, and in 2015, was listed on Forbes 30 under 30 in Science as one of the “most disruptive, game-changing and innovating young personalities in science.” In 2016, Elizabeth founded Women in Chemical Engineering (WChE), an organization focused on empowering, strengthening, and promoting the network of femme chemical engineers across all levels. She received the Association for Women in Science Early Career Achievement in STEM award, among others for her scientific and outreach work.

About UQ Centre for Clinical Research Seminars

The UQ Centre of Clinical Research (CCR) Seminars are held fortnightly on Wednesdays from 12pm - 1pm (except during school holidays) in the CCR Auditorium, Herston. The series features topics in the  field of research, presented by invited international, interstate and local researchers.