Probing sepsis and acute inflammation using ICAM-1 specific mSPIO 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 sepsis is resultant of acute inflammation, we propose using magnetic resonance imaging (MRI) to quantitatively observe a patient's degree of inflammation as an indicator of sepsis progression. By quantitatively tracking the biodistribution of nanomicelle encapsulating superparamagnetic iron oxide (mSPIO) nanoparticles specific to intercellular adhesion molecule 1 (ICAM-1), an adhesion molecule which displays distinct spatiotemporal response to inflammation, we have found that septic in vivo mouse subjects showed greater mSPIO accumulation in the liver than that of non-septic and non-ICAM-1 specific controls, demonstrating the utility of MRI-based detection as a diagnosis method for sepsis.