Probing sepsis and sepsis-like conditions using untargeted SPIO nanoparticles

Abstract

Sepsis is the leading cause of death in critically ill patients in the United States. Current diagnosis of sepsis relies heavily on the patient's manifestation of septic symptoms, which occur at life-threatening late stage of sepsis. Because the underlying biological changes of sepsis occur hours to days before the clinical presentation of symptoms, early detection of the biological changes will provide crucial opportunities for early diagnosis and effective treatment of sepsis. As an candidate for early sepsis detection, we propose using a novel quantitative susceptibility mapping (QSM) MRI that quantifiably measure the activity of the immune system during sepsis progression. It has been observed that Kupffer cells, comprising 80% of the liver's macrophages, play a pivotal role in the early response to system infection, a condition characteristic of sepsis. Further, it has been observed that phagocytosis by Kupffer cells is a major mechanism by which nanoparticle-based contrast agents, such as Feridex, are cleared from the body. By quantifying the amount of superparamagnetic iron-oxide nanoparticles uptaken by these macrophages and correlating this result to immune system response and the progression of sepsis, we can utilize commonly used contrast agents as markers in monitoring and diagnosing sepsis condition. This study offers an in vitro proof of concept; RAW264.7 murine monocytes were treated with lipopolysaccharide to induce a sepsis-like cell condition, incubated with the FDA-approved contrast agent Feridex IV, and imaged using QSM MRI for the quantification of iron.