Development Platform for Analysis of NIR-mediated Exosomal Micro Carriers
Abstract
We propose to purchase a ZetaView Multiple Parameter Particle Tracking Analyzer Platform and an Optima Max-XP Tabletop Ultracentrifuge for Integrated NIHL Research Group to enhance our ongoing study in the analysis of Exosomal micro carriers. This platform will enhance the research quality and research-related advancements in the hot topic area of exsosome research associated with basic mechanisms of oxidative stress. Currently there are four ONR-funded research projects that would benefit from this critically important research platform. The platform will enhance research capabilities and accelerate basic investigations in the field of leading edge hearing loss research, synthetic biology, undersea medicine as well as precision medicine. This technology will contribute to comprehensive understanding of cell signaling pathways and biomolecular function. The understanding of this interplay and the means to address it to investigate the prevention of the occurrence of NIHL will seamlessly integrate with our existing analytical systems. The equipment will portal to the existing ONR funded NIR platform and will be integrated to the cellular analysis side of the platform in which metabolomics and proteomic analysis are currently performed. The ZetaView Multiple Parameter Particle Tracking Analyzer Platform and an Optima Max-XP Tabletop Ultracentrifuge would enhance by at least an order of magnitude the analytical capacity and expand our capability to investigate these new pathways under intense investigation.Our antioxidant-enhanced exosome drug delivery research investigations have recently shown promising results, but characterization and isolation of exosomes need unique and cutting-edge tools represented by this application permit for standard GMP/GLP regulations and proper quality control for correct approach. The Noise-Induced Hearing Loss Research Group have been investigated antioxidant administration as a therapeutic tool for hearing loss (Grondin et al Hear Res. 2013). Exosomal engineering and therapeutic delivery of antioxidant to recipient auditory cell might be a powerful tool to mitigate oxidative stress and cochlear inflammation, the main cause of noise induced hearing loss. Our preliminary data shows that antioxidant treatment in high concentrations could lead to exosome formation from auditory cells, and these powerful engineered extracellular vesicles act as nanoencapsulated drug delivery shuttles and they mitigate reactive oxygen species and mitochondrial superoxide level on recipient sensory cells. Our results show that antioxidant enhanced exosomes modulating redox balance and directly suppress oxidative stress response in HEI-OC1 cells. The efficient internalization of antioxidant enhanced exosomes in auditory cells makes it a suitable to deliver antioxidant cargo in sensory cells during gentamicin induced ototoxic damage.The proposed exosomal characterization platform???s main objective is to analyze and characterize exosomes and their role in the molecular pathways in NIHL, also the anti-inflammatory effect and molecular target of NIR exposure. The requested instrument platform gives us a unique tool to phenotype exosomal system response during NIHL, and to characterize multiplex inflammasome and mitochondrial protein targets, fundamental to our understanding of the physio biochemical interactions leading to NIHL.The ZetaView Multiple Parameter Particle Tracking Analyzer Platform and an Optima Max-XP Tabletop Ultracentrifuge for Integrated NIHL Research is an absolutely critical tool to be used for the examination of exosome mediated cochlear drug delivery.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 19, 2018
- Source ID
- N000141812849
Entities
People
- Rick Rogers
Organizations
- Office of Naval Research
- President and Fellows of Harvard College
- United States Navy