Journal
MACROMOLECULAR BIOSCIENCE
Volume 20, Issue 2, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201900279
Keywords
dual-modality imaging; molecular imaging; nanoparticles; osteopontin; vulnerable plaques
Funding
- National Nature Science Foundation of China [81530058, 81570272, 81571841, 81601557, 81820108019]
- National Key Research Program of China [2016YFB0303303]
- Translational Medicine Project of Chinese PLA General Hospital [2017TM-003]
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Because of the high mortality of coronary atherosclerotic heart diseases, it is necessary to develop novel early detection methods for vulnerable atherosclerotic plaques. Phenotype transformation of vascular smooth muscle cells (VSMCs) plays a vital role in progressed atherosclerotic plaques. Osteopontin (OPN) is one of the biomarkers for phenotypic conversion of VSMCs. Significant higher OPN expression is found in foam cells along with the aggravating capacity of macrophage recruitment due to its arginine-glycine-aspartate sequence and interaction with CD44. Herein, a dual-modality imaging probe, OPN targeted nanoparticles (Cy5.5-anti-OPN-PEG-PLA-PFOB, denoted as COP-NPs), is constructed to identify the molecular characteristics of high-risk atherosclerosis by ultrasound and optical imaging. Characterization, biocompatibility, good binding sensibility, and specificity are evaluated in vitro. For in vivo study, apolipoprotein E deficien (ApoE(-/-)) mice fed with high fat diet for 20-24 weeks are used as atherosclerotic model. Ultrasound and optical imaging reveal that the nanoparticles are accumulated in the vulnerable atherosclerotic plaques. OPN targeted nanoparticles are demonstrated to be a good contrast agent in molecular imaging of synthetic VSMCs and foam cells, which can be a promising tool to identify the vulnerable atherosclerotic plaques.
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