Biodegradable gold nanoparticles as contrast agents for CT

PROJECT SUMMARY Computed tomography is used in about million imaging studies per year in the USA Iodinated contrast agents are used in roughly half of these studies Computed tomography is particularly important for the diagnosis of coronary artery disease where it depends on the use of iodinated contrast agents to visualize the arteries However these agents have a number of shortcomings such as short circulation times causing allergic reactions and contrast induced nephropathy The latter condition results in higher morbidity mortality and costs and is most common in patients with poor kidney function The proportion of patients over with kidney disease is This percentage is rapidly rising since the incidence of diabetes is rapidly increasing projected to affect of the US population by and kidney disease is a common complication of diabetes The risk of cardiovascular disease is trebled for diabetics Therefore there is a growing population that will suffer cardiovascular disease but for whom the current diagnostic agents can be harmful creating a pressing need for new CT contrast agents Others and we have shown gold nanoparticles to be highly effective biocompatible CT contrast agents that have long circulation times However gold nanoparticles are typically very slowly excreted leading to the risk of long term toxicities and would preclude FDA approval Penn faculty together with PolyAurum LLC propose to address this issue via development of biodegradable gold nanoparticles We have chosen a comparatively simple yet flexible nanoparticle design in order to improve the likelihood of translation The nanoparticles should circulate in the blood for some hours before gradually breaking down into their components for renal excretion Rapid excretion should be avoided to prevent a burden on the kidneys but excretion should be reasonably fast to avoid the potential for long term safety issues and confounding follow up imaging studies We will therefore study how to tune degradation to occur over hours We will confirm the biocompatibility of the new formulations in vitro We will then ensure that the new formulation provides excellent in vivo CT contrast as well as determining in vivo biocompatibility and excretion After these experiments we will be well placed to raise additional funds to complete toxicology screening to allow us to apply for investigational new drug IND status Approval of the IND application would set the stage for clinical trials of the formulation PUBLIC HEALTH RELEVANCE Computed tomography is vital for cardiovascular imaging It relies on iodinated small molecule contrast agents however these iodinated agents have many drawbacks including short circulation times allergic reactions and causing kidney damage in some patients We are developing long circulating biodegradable gold nanoparticle CT contrast agents to potentially replace these iodinated agents for this at risk patient population