A neutrophil-mimetic magnetic nanoprobe for molecular magnetic resonance imaging of stroke-induced neuroinflammation

Abstract

Neuroinflammation plays a key role in the progression of brain injury induced by stroke, and has become a promising target for therapeutic intervention for stroke. Monitoring this pivotal process of neuroinflammation is highly desirable to guide specific therapy. However, there is still a lack of a satisfactory nanoprobe to selectively monitor neuroinflammation. As endothelial cell activation is a hallmark of neuroinflammation, it would be clinically relevant to develop a non-invasive in vivo imaging technique to detect the endothelial activation process. Herein, inspired by the specific neutrophil–endothelium interaction, we designed neutrophil-camouflaged magnetic nanoprobes (NMNPs) that can be used to target activated endothelial cells for improved neuroinflammation imaging. NMNPs are composed of an inner core of superparamagnetic iron oxide (SPIO)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and a biomimetic outer shell of a neutrophil membrane, which maintained the biocompatibility and targeting ability of neutrophils and the excellent contrast effects of SPIO. Moreover, we demonstrated that NMNPs can successfully bind to inflamed cerebral vasculature using the intravital imaging of live cerebral microvessels in transient middle cerebral artery occlusion (tMCAO) mice. After that, NMNPs could further accumulate in the brain vasculature and exhibit excellent contrast effects for stroke-induced neuroinflammation and biosafety. We believe that the neutrophil-camouflaged magnetic nanoprobe could serve as a highly safe and selective nanoprobe for neuroinflammation imaging and has alluring prospects for clinical application.