A Folate-Conjugated Dual-Modal Fluorescent Magnetic Resonance Imaging Contrast Agent That Targets Activated Macrophages In Vitro and In Vivo

作者：Yao, Yuyu^*; Li, Bing; Yin, Chao; Cong, Fu; Ma, Gen-Shan; Liu, Nai-Feng; Fan, Qu-Li^*; Teng, Gao-Jun^*

来源：Journal of Biomedical Nanotechnology, 2016, 12(12): 2161-2171.

DOI：10.1166/jbn.2016.2316

• Atherosclerotic Plaque
• Magnetic Resonance Imaging
• Folate Receptor beta
• Fluorescent Magnetic Nanoparticles
• Macrophages

Folate receptor (FR)-targeted, dual-modal fluorescent iron oxide magnetic nanoparticles (MNPs) with amphiphilic asymmetric shells that terminate with folic acid (MNPs@OPE-PEG-FA) and non-targeting MNPs@OPE-PEG-NH2 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, macrophage-derived RAW264.7 cells and in vivo partial ligation of left carotid arteries in apoE(-/-) mice. 7.0T magnetic resonance imaging (MRI) of MNPs@OPE-PEG-FA and MNPs@OPE-PEG-NH2 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-beta and macrophage marker were detected by immunohistochemistry. RAW264.7 cells accumulated more MNPs@OPE-PEG-FA than MNPs@OPE-PEG-NH2. Inversely proportional loss of MRI signal intensity showed that carotid plaques absorbed significantly more injected MNPs@OPE-PEG-FA than MNPs@OPE-PEG-NH2. The MNPs@OPE-PEG-FA probe was shown to be an effective 2-photon fluorescent plaque imaging agent in vitro and ex vivo. It detects FR-beta-enriched inflammatory plaques and has potential utility for monitoring atherosclerotic plaques.

• 出版日期2016-12
• 单位东南大学; 南京邮电大学