CAREER: Understanding Dynamics of Ultra-small Magnetic Nanoparticles in the Brain for Neuron Regeneration Therapies

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This Faculty Early Career Development Program (CAREER) project will create new understanding of an innovative treatment for neurodegenerative diseases (i.e., Alzheimer's and Parkinson's) and promote the progress of science and advance the national health. Neurodegenerative disease, resulting from the progressive loss of neurons, takes a devastating toll on the aging population in the U.S. Recent advances in magnetically driven biodegradable ultra-small nanoparticles offer opportunities in transformational non-invasive neuron regeneration treatments. This innovative technology holds great potential to usher biotechnology into a new era of precision medicine and tissue engineering. However, to date, neuroscientists have largely focused on the associated biological phenomena, with little attention to microvascular dynamics of nanoparticle transport, thus limiting the translation to clinical practice. The microvascular dynamic model, established from this research will be capable of quantifying the neuron regeneration process. This is essential for overcoming intrinsic trial-and-error approaches and for moving closer to clinical success. Additionally, the education and outreach activities of the project will advance awareness of nanotechnology and biomedicine, and will increase the participation of historically underrepresented groups in STEM, including women, and first-generation college students in the greater Long Island. The research objective of this CAREER project is to employ analytical perturbative and continuation approaches to analyze biological phenomena to yield a rich harvest of predictive insights into the microvascular dynamics of ultra-small nanoparticles transport in a brain microenvironment. The research plan is to first create two dynamic models: one will capture the magnetic transport behavior of ultra-small nanoparticles within a microvasculature; the other will describe cytoskeleton dynamics within brain microvascular networks. Combined, a microvascular dynamic model of nanoparticle transport will be established to discern which parameters are needed for directing target-selective magnetic stimulation to produce a reliable and steady therapeutic tool by applying a pre-defined magnetic field on the nanoparticles. For the first time, cytoskeleton dynamics associated with growing neurons will be analyticaly modeled by perturbing a nanoparticle diffusing in a potential well with a slowly drifting minimum position. Importantly, this model will be constructed to track the individual growing behaviors of thousands of neurons, and perform high-throughput/low-cost sensitivity analyses to identify the key parameters in a complex brain microenvironment. Furthermore, combined with recent advances in power electronics, this project holds a high potential for contributing to the development of a new microchip that improves researcher capacity for studying the growth behavior of the neuron cells inside a three dimensional extracellular matrix.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.