Nanoengineered Neutrophil asF-MRI Tracer for Alert Diagnosis and Severity Assessment of Acute Lung Injury.

Abstract

Acute lung injury (ALI) is a severe complication in clinical settings. Alert diagnosis and severity assessment of ALI is pivotal to ensure curative treatment and increase survival rates. However, the development of a precise ALI diagnostic strategy remains a pending task. Here, leveraging neutrophil's inflammation-homing and physiological barrier-navigating capability, a facile strategy is proposed for achieving targetedF-MRI detection of ALI based on the nanoengineered neutrophil internalized with perfluorocarbon nanoemulsion (Neu@PFC). The remodeling process poses a negligible impact on the neutrophil's inherent activation and transmigration functions. The migratory behavior of Neu@PFC toward pneumonia is confirmed in vivo using an LPS-induced ALI murine model. Direct intratracheal (i.t.) administration contributes to a vast deposition of Neu@PFC within the lung, allowing for real-timeF-MRI visualization and the potential to predict progressive pneumonia. Furthermore, intravenous (i.v.) administration of Neu@PFC enables quantitative assessment of the extent of ALI due to the chemokine-guided neutrophil migration. This study not only provides a pathway to diagnose ALI, but also sheds light on the neutrophil recruitment and activation cues in different tissues and inflammatory conditions, which is a prerequisite for developing potential therapeutic approaches.