A Folate-Conjugated Dual-Modal Fluorescent Magnetic Resonance Imaging Contrast Agent That Targets Activated Macrophages In Vitro and In Vivo
Folate receptor (FR)-targeted, dual-modal fluorescent iron oxide magnetic nanoparticles (MNPs) with amphiphilic asymmetric shells that terminate with folic acid ([email protected]) and non-targeting [email protected]2 nanoparticles were used to examine inflammation-associated activated macrophages within carotid atherosclerotic plaques in apolipoprotein E–deficient (apoE–/–) mice. Experiments included in vitro iron oxide uptake in FR-positive, macrophagederived RAW264.7 cells and in vivo partial ligation of left carotid arteries in apoE–/– mice. 7.0T magnetic resonance imaging (MRI) of [email protected] and [email protected]2 treatment groups (6 mice/group) was performed before and 24 h after contrast administration. MNPs deposition was confirmed using Prussian blue staining and macrophage cells expressing FR-β and macrophage marker were detected by immunohistochemistry. RAW264.7 cells accumulated more [email protected] than [email protected]2. Inversely proportional loss of MRI signal intensity showed that carotid plaques absorbed significantly more injected [email protected] than [email protected]2. The [email protected] probe was shown to be an effective 2-photon fluorescent plaque imaging agent in vitro and ex vivo. It detects FR-β-enriched inflammatory plaques and has potential utility for monitoring atherosclerotic plaques.
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Document Type: Research Article
Publication date: December 1, 2016
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