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Multifunctional nanoparticles for detection, quantification, and treatment of endothelial erosions in experimental atherosclerosis
Author(s) -
Pan Hua,
Allen John S,
Yanaba Noriko,
Schlesinger Paul H,
Wickline Samuel A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.888.3
Subject(s) - in vivo , inflammation , endothelium , medicine , endothelial dysfunction , pathophysiology , pathology , vulnerable plaque , endothelial activation , evans blue , chemistry , pharmacology , immunology , biology , microbiology and biotechnology
Acute atherothrombotic occlusion in heart attack and stroke implies disruption of the vascular endothelial barrier that exposes a highly procoagulant intimal milieu. However, the evolution, severity, and pathophysiological consequences of vascular barrier damage in advanced atherosclerotic plaque remain unknown, in part because quantifiable methods and experimental models are lacking for its in vivo assessment. Here, we report a multifunctional perfluorocarbon (PFC) nanoparticle (NP) for delineation of endothelial erosions as well as targeted antiinflammatory drug delivery to the erosion site. Detection and quantification (MRS and fluorescence imaging, shown in Figure) of endothelial erosions were evaluated in ApoE−/− mice fed a high fat diet for 4 – 7 months. Endothelial barrier disruption was apparent from massive and rapid passive permeation and intimal trapping of PFC nanoparticles (~250nm diameter) that normally do not penetrate intact endothelial barriers after in vivo circulation for 2 hours. RT‐PCR (CCL2, Npy) and immunohistological (I‐kB protein)results suggested that treatment (6 doses, i.v. every other day) PFC nanoparticles loaded with NF‐kB inhibitors (NEMO binding domain peptides) in 4 month fed ApoE−/− mice downregulated inflammation in aortas. Accordingly, PFC NP may be useful for defining disease stage and for following therapy to heal unstable plaques.