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 T 1-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.
Highlights
Sepsis is a type of systemic in ammatory response syndrome induced by infections, and is becoming a major cause of admission to the intensive care unit with a high in-hospital mortality rate
Using MRET, activatable magnetic resonance imaging (MRI) probes have been designed for pH imaging and T1–T2 dual modality imaging.[48,49,50,51]. Inspired by these signi cant ndings, we present the rational design of novel reactive oxygen species (ROS)-activatable nanoprobes (ROS CAs) composed of a clinically approved iron oxide core, Gd–DTPA, and hyaluronic acid (HA) that could image ROS down to sub-micromolar concentrations via MRI, and use them as sensitive contrast agents for sepsis evaluation
The above data provided detailed changes of surface functional groups and electric charge during the synthesis process of rational design of novel activatable nanoprobes (ROS CAs). Both the TEM image and structural information of ROS CAs indicated that they were highly monodisperse with excellent size uniformity as well as their average diameter could be measured as 15 nm (Fig. 2e)
Summary
In the development of sepsis, the activation of the host immune system triggered by serious infection usually causes a systemic in ammation response.[12]. Different from exogenous probes which can be used to diagnose diseases by comparing signal changes before and a er administration, endogenous probes are susceptible to various non-ROS factors, such as the changes in the contents of oxygen and water.[42,43,44] exogenous 19F-MRI probes have emerged as contrast agents for in vivo ROS imaging.[45,46] they require the use of the 19F-MRI technique, which is limited by the lack of speci c clinical scanners as most of them are only designed for 1H use.[47] the rational design of novel activatable probes to detect systemic ROS for the evaluation of sepsis and the study of sepsis and related ROS biology is still highly needed. We hope that the present study provides a new strategy to aid in the early diagnosis and risk assessment of sepsis, and offers a valuable insight for the extensive study of sepsis and ROS biology
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