This project is concerned with the synthesis and characterization of multifunctional nanoparticles for cancer diagnosis and therapy. These nanoparticles include several layers: a superparamagnetic iron oxide core, a silica layer, a gold shell, and a coating of polyethylene glycol (PEG).The magnetic core provides enhanced contrast for magnetic resonance imaging and the ability to be heated by alternating magnetic fields, destroying tumors by hyperthemia. The gold shell facilitates optical imaging, and can be heated by near infrared radiation, providing cancer therapy by photothermal ablation. The silica layer suppresses aggregation of the magnetic nanoparticles and mediates the particle?s optical properties. The PEG coating provides a biocompatible surface that can be further biofunctionalized with targeting ligands.
The intellectual merit of this research lies in the fact that several project activities will, if successful, represent groundbreaking accomplishments. The project involves an interplay of nanoparticle synthesis and characterization of biological systems in which these nanoparticles are loaded. A process is being developed in which three-layer nanoparticles are produced by a sequence of vapor-phase processes that constitute a nanoparticle manufacturing assembly line in which the dimensions and composition of each layer are controlled to nanoscale tolerances. In close interaction with these synthesis studies, studies are conducted of the uptake, properties and behavior of these nanoparticles in biological tissue.
If successful the project will constitute several breakthroughs: a new methodology for production of multilayer nanoparticles by a sequence of gas-phase processes; the first Raman imaging of gold-shell nanoparticle uptake in cells that avoids the use of molecular labels; the first measurement of laser heat generation in nanoparticle-laden biological systems to correlate optical and thermal approaches at scales ranging from sub-cellular to tissue; the first method to link heat generation to the number of nanoparticles per cell, thereby suggesting a simple optical method for determining nanoparticle uptake in cells.
The project involves a collaboration that brings together expertise in nanoparticle synthesis and processing by aerosol routes with expertise in heat and mass transfer in biological systems. This work is highly interdisciplinary, involving particulate and multiphase processes, nanomanufacturing, bioengineering, biomaterials, thermal and mass transport sciences, optics and chemistry.
The project has several broader impacts. This project is developing tools that may one day constitute a major advance in the treatment of cancer. More broadly, this project will lead to greater understanding of the interactions of nanoparticles with biological systems. The nanoparticle manufacturing assembly line could constitute a prototype for producing multifunctional nanoparticles for other types of applications, for example in energy conversion. This project involves two graduate students in a highly interdisciplinary environment. The PIs have a strong record of involving women and other under-represented groups, as well as undergraduates, in their research, and are continuing to do so in this project. Finally, the PIs have been active in several programs involving outreach to K-12 students and the broader public, and the broader public, and outreach activities of this type will be enriched by the interdisciplinary project.
