At a fundamental level, nanomedicine, in which in which tailor-made nanoparticles are used to treat or diagnose disease, and nanotoxicology, in which the health effects of nanoparticles are of concern, examine the interaction between nanoparticles and biomolecular structures within the human body, in particular with proteins. Of considerable interest in both fields is the process of opsonization, in which blood proteins bind to nanoparticles, eventually resulting in an immunological response within the body. A major roadblock to development in nanomedicine and nanotoxicology at the fundamental level is the dearth of analysis techniques available for nanoparticles from which nanoparticle properties relevant to their interactions with biological systems can be inferred. The research team at the University of Minnesota in collaboration with a team at TSI Incorporate will develop two new measurement systems specifically designed to examine the binding of chosen proteins to inorganic nanoparticles. Both systems will make use of aerosol measurement instrumentation, specifically, an electrospray aerosol generator to aerosolize nanoparticle-protein complexes from an in-vitro model system, allowing for measurement of their size distribution with a differential mobility analyzer (DMA) and condensation particle counter. In the first proposed system, an inductively coupled mass spectrometer will be developed and used to determine the size of the inorganic nanoparticle core within the protein nanoparticle complexes, allowing for inference of the number of proteins bound to nanoparticles as a function of nanoparticle size and chemical composition. In the second system, DMA size classified nanoparticle-protein complexes will be analyzed by hydrogen-deuterium exchange, using a newly developed micro-Particle-into-Liquid Sampler and electrospray mass spectrometry. This system will allow for determination of the site on a protein where binding to nanoparticles occurs, which is not possible with available instrumentation. When used in tandem, these two new systems will allow for a new method of nanoparticle characterization specific for nanomedicine and nanotoxicology, allowing for transformative research in these fields as well as in nanoparticle science and engineering.
A key issue in developing next generation medical technologies is improving our understanding of how nanomaterials interact with the basic building blocks of life, namely, proteins. To address this issue, new measurement technologies and collaborative efforts between researchers in academia and in industry will be necessary. Professors Hogan and Bischof of the University of Minnesota, in collaboration with Dr. Farmer of TSI Incorporated plan to develop two transformative measurement systems designed specifically to monitor the interactions between proteins and nanomaterials. These two measurement systems will enable scientists, engineers, and physicians to determine, for the first time, the precise properties of specific nanomaterials which facilitate their interactions with biological molecules, and similarly, which molecules within the body interact with nanomaterials. The collaborative research activities will involve students and faculty at the University of Minnesota as well as staff scientists at TSI Incorporated. The proposed activities will result not only in the development of two measurement systems available for wide distribution, but also new measurements of the interactions between nanoparticles and biological systems at the molecular level.