Recently, there has been growing interest in the use of gold nanoparticles (GNPs) as contrast agents for x-ray computed tomography (CT) imaging applications. This is largely because gold provides almost three times greater X-ray attenuation per unit weight than iodine and GNPs generally exhibit significantly longer circulation times than tri-iodobenzene adducts. These beneficial properties have allowed GNPs to be used as both blood pool and targeted imaging agents in animal models. Although the results have been promising, GNPs suffer from protracted elimination from the liver. For example, it has been found that there is only a 9% fall in the content of gold in the liver from day 1 to 6 months, following the intravenous injection of 40nm GNPs. These findings are likely to present a major impediment for clinical translation. Whole-body clearance can be improved with 1.9nm GNPs, since they are small enough to undergo glomerular filtration;however, these smaller GNPs have shorter circulation times and possess a smaller cross-sectional area and shorter path length for x-ray attenuation. Therefore, they are expected to be less favorable for CT angiography and targeted imaging studies, where the number of GNPs capable of attenuating x-rays is limited by the number of cell surface receptors at the target site. The overall goal of this proposal is to develop biodegradable GNPs that can be efficiently excreted, while still possessing geometric dimensions that are favorable for CT angiography and targeted imaging studies.
The specific aims for this proposal are (1) Synthesize and characterize gold-loaded polymeric micelles (GPMs) with various physical and chemical properties;(2) Evaluate the biodistribution, circulation time, and retention of GPMs;and (3) Characterize the targeting capabilities of anti-HER2-affibody conjugated GPMs.
The overall goal of this proposal is to develop an x-ray contrast agent based on gold nanoparticles that can be efficiently degraded and excreted, while still possessing geometric dimensions that are favorable for CT angiography and targeted imaging studies. We hope that our new nanoparticle design will provide a means to reduce the long-term retention of gold within the liver and other organs, and ultimately facilitate clinical translation.
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