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Ultraselective Carbon Nanotubes for Photoacoustic Imaging of Inflamed Atherosclerotic Plaques
Author(s) -
Gifani Mahsa,
Eddins Devon J.,
Kosuge Hisanori,
Zhang Yapei,
Paluri Sesha L. A.,
Larson Timothy,
Leeper Nicholas,
Herzenberg Leonore A.,
Gambhir Sanjiv Sam,
McConnell Michael V.,
Ghosn Eliver E. B.,
Smith Bryan Ronain
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202101005
Subject(s) - ex vivo , flow cytometry , photoacoustic imaging in biomedicine , in vivo , pathology , vulnerable plaque , immune system , fibrous cap , inflammation , medicine , myocardial infarction , preclinical imaging , macrophage , immunology , in vitro , biology , cardiology , biochemistry , physics , microbiology and biotechnology , optics
Disruption of vulnerable atherosclerotic plaques often leads to myocardial infarction and stroke, the leading causes of morbidity and mortality in the United States. A diagnostic method that detects early‐stage high‐risk atherosclerotic plaques could prevent these sequelae. The abundant immune cells in the arterial wall, especially inflammatory Ly‐6C hi monocytes and foamy macrophages, are indicative of plaque inflammation, and may be associated with plaque vulnerability. Hence, a new method is sought to develop that specifically targets these immune cells to offer clinically relevant diagnostic information about cardiovascular disease. Ultraselective nanoparticle targeting of Ly‐6C hi monocytes and foamy macrophages and clinically‐viable photoacoustic imaging (PAI) are combined in order to precisely and specifically image inflamed plaques ex vivo in a mouse model that mimics human vulnerable plaques histopathologically. Within the plaques, high‐dimensional single‐cell flow cytometry (13‐parameter) shows that the nanoparticles are almost‐exclusively taken up by the Ly‐6C hi monocytes and foamy macrophages that heavily infiltrate plaques. PAI identifies inflamed atherosclerotic plaques that display ≈6‐fold greater signal compared to controls ( P < 0.001) 6 h after intravenous injection of ultraselective carbon nanotubes, with in vivo corroboration via optical imaging. This highly‐selective strategy may provide a targeted, noninvasive imaging strategy to accurately identify and diagnose inflamed atherosclerotic lesions.