EAGER: Low-level detection of complex nanomaterials in biological media

This project will focus on proof-of-concept research applying Accelerator Mass Spectrometry (AMS) for low-level detection of complex nanomaterials in biological media. A successful project will enable major improvements in mechanistic studies of the fate and transport of complex engineered nanomaterials (ENMs as nanoparticles) in environmental, health and safety studies. AMS can separate rare isotopes with high selectivity and high sensitivity. In this proposal, complex ENMs are defined as nanoparticles with one material as their core and different surface-bound molecules (hereafter referred to as coatings) to assist their performance in applications. Complex ENM nanoparticles often agglomerate during environmental and biological testing, both the core and coating may be transformed by such exposures, and material balances need to be performed on both the core and coatings materials in order to properly interpret their transport and transformations over the product life cycles. The research team has recently synthesized complex ENMs containing different rare isotopes in the core and the coating. Two pathways are proposed: 1) the synthesis and testing of a complex ENM system, an 26Al-labeled alumina core (Al2O3) with 14C-labeled coatings (citric acid), which will be tested at low dose levels in a rat model and 2) the synthesis and biodegradation evaluation of both a core material, 32Si-labeled mesoporous silica, and a coating material, 14C-labeled PLGA. Pathway 1 work will attempt to demonstrate the lower limits of detection of the AMS method, which is expected to be 103 to 109 times more sensitive that radioactivity detection. Pathway 2 work will provide an experimental system for explicit testing of degradable cores and coatings. As these rare isotopes (RI) can be detected near attomole levels using AMS, it should be possible to identify any changes in the molar ratios (coating RI/ENM RI) during dosing, cell uptake, coating by environmental chemicals, transformations in cell, or in the environment. Transformational testing will be done in another, follow-on, project. Intellectual merit. A successful study will develop rare isotope AMS, a method with high sensitivity and high selectivity, as a platform technology for measurement of complex ENM transformations in relevant media. AMS should be particularly valuable in determining the long-term fate of complex ENMs in biological and environmental media, especially if the ENMs are aggregated or agglomerated. These test systems will address ENM measurement infrastructure needs specified in the NNI 2011 EHS Research Strategy Needs report. Broader impact. A successful proposal will stimulate and support the development and dissemination of next-generation instrumentation and multiuser facilities, specifically, the application of AMS methods to EHS studies of nanomaterial toxicology. The investigators will continue their current activities in education and training, and will include the new methodology in EGR 780, Characterization of nanomaterials for medical applications, is a new course supporting our Cancer Nanotechnology Training Center, an 26Al-labeled NIH-funded program