Ultrasensitive magnetic resonance imaging of systemic reactive oxygen species in vivo for early diagnosis of sepsis using activatable nanoprobes

Abstract

Current diagnostic methods for sepsis lack required speed or precision, often failing to make timely accurate diagnosis for early medical treatment. The systemic excess generation of reactive oxygen species (ROS) during sepsis has been considered as an early indicator of sepsis. Herein, we present the rational design of novel activatable nanoprobes (ROS CAs) composed of a clinically approved iron oxide core, Gd–DTPA, and hyaluronic acid (HA) that can image ROS down to sub-micromolar concentrations via magnetic resonance imaging (MRI), and use them as sensitive contrast agents for sepsis evaluation. Such a well-defined nanostructure allows them to undergo ROS-triggered degradation and release Gd–DTPA in the presence of ROS, leading to the recovery of the quenched T₁-weighted MRI signal with fast response. With outstanding sensitivity and unlimited tissue penetration depth, ROS CAs are capable of imaging systemic ROS overproduction in mice with early sepsis. Moreover, by using these well-prepared ROS CAs, the severity of the sepsis can be rapidly evaluated by monitoring the systemic ROS levels in vivo. Overall, the present study will not only provide a new strategy to aid in the early diagnosis and risk assessment of sepsis, but also offer valuable insight for the study of sepsis and ROS biology.