Detection of gold nanorods uptake by macrophages using scattering analyses combined with diffusion reflection measurements as a potential tool for in vivo atherosclerosis tracking

In this study, we report a potential noninvasive technique for the detection of vulnerable plaques using scatter analyses with flow cytometry (FCM) method combined with the diffusion reflection (DR) method. The atherosclerotic plaques are commonly divided into two major categories: stable and vulnerable. The vulnerable plaques are rich with inflammatory cells, mostly macrophages (MΦ), which release enzymes that break down collagen in the cap. The detection method is based on uptake of gold nanorods (GNR) by MΦ. The GNR have unique optical properties that enable their detection using the FCM method, based on their scattering properties, and using the DR method, based on their unique absorption properties. This work demonstrates that after GNR labeling of MΦ, 1) the FCM scatter values increased up to 3.7-fold with arbitrary intensity values increasing from 1,110 to 4,100 and 2) the DR slope changed from an average slope of 0.196 (MΦ only) to an average slope of 0.827 (MΦ labeled with GNR) (P<0.001 for both cases). The combination of FCM and DR measurements provides a potential novel, highly sensitive, and noninvasive method for the identification of atherosclerotic vulnerable plaques, aimed to develop a potential tool for in vivo tracking.

[1]  Dror Fixler,et al.  Reflected light intensity profile of two-layer tissues: phantom experiments. , 2011, Journal of biomedical optics.

[2]  Konstantin Sokolov,et al.  Preventing protein adsorption and macrophage uptake of gold nanoparticles via a hydrophobic shield. , 2012, ACS nano.

[3]  T. Lehtimäki,et al.  Early childhood hospitalisation with infection and subclinical atherosclerosis in adulthood: the Cardiovascular Risk in Young Finns Study. , 2015, Atherosclerosis.

[4]  I. Heimbeck,et al.  Standardized single‐platform assay for human monocyte subpopulations: Lower CD14+CD16++ monocytes in females , 2010, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[5]  Zeev Zalevsky,et al.  In vivo tumor detection using polarization and wavelength reflection characteristics of gold nanorods. , 2013, Nano letters.

[6]  V. Fuster,et al.  Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis. , 2009, JACC. Cardiovascular imaging.

[7]  H. Weintraub,et al.  Identifying the vulnerable patient with rupture-prone plaque. , 2008, The American journal of cardiology.

[8]  R. Kanwar,et al.  Emerging engineered magnetic nanoparticulate probes for targeted MRI of atherosclerotic plaque macrophages. , 2012, Nanomedicine.

[9]  Hamidreza Ghandehari,et al.  Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[10]  Dror Fixler,et al.  Nanoparticle uptake by macrophages in vulnerable plaques for atherosclerosis diagnosis , 2015, Journal of biophotonics.

[11]  J. Schwitter,et al.  MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial. , 2013, European heart journal.

[12]  M. El-Sayed,et al.  Why gold nanoparticles are more precious than pretty gold: noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes. , 2006, Chemical Society reviews.

[13]  Menachem Motiei,et al.  Intercoupling surface plasmon resonance and diffusion reflection measurements for real‐time cancer detection , 2013, Journal of biophotonics.

[14]  W. Rostène,et al.  Effects of Benzalkonium Chloride on THP-1 Differentiated Macrophages In Vitro , 2013, PloS one.

[15]  G. Heine,et al.  Monocyte subsets in atherosclerosis , 2014, Hämostaseologie.

[16]  Mostafa A. El-Sayed,et al.  Preparation and Growth Mechanism of Gold Nanorods (NRs) Using Seed-Mediated Growth Method , 2003 .

[17]  Hamootal Duadi,et al.  In‐vivo Tumor detection using diffusion reflection measurements of targeted gold nanorods – a quantitative study , 2012, Journal of biophotonics.

[18]  Warren C W Chan,et al.  Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. , 2007, Nano letters.

[19]  A. Tárnok,et al.  OMIP‐023: 10‐Color, 13 antibody panel for in‐depth phenotyping of human peripheral blood leukocytes , 2014, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[20]  P. Jain,et al.  Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine. , 2006, The journal of physical chemistry. B.

[21]  I. Roifman,et al.  Chronic inflammatory diseases and cardiovascular risk: a systematic review. , 2011, The Canadian journal of cardiology.

[22]  Josse De Baerdemaeker,et al.  Spatially resolved diffuse reflectance in the visible and near-infrared wavelength range for non-destructive quality assessment of ‘Braeburn’ apples , 2014 .

[23]  Ralph Weissleder,et al.  Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques , 2013, Circulation research.

[24]  Kim Van der Heiden,et al.  Folate Receptor–Targeted Single-Photon Emission Computed Tomography/Computed Tomography to Detect Activated Macrophages in Atherosclerosis: Can It Distinguish Vulnerable from Stable Atherosclerotic Plaques? , 2014, Molecular imaging.

[25]  Arezou A Ghazani,et al.  Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. , 2006, Nano letters.

[26]  V. Karagkiozaki Nanomedicine highlights in atherosclerosis , 2013, Journal of Nanoparticle Research.

[27]  W. Boyes,et al.  Detection of silver nanoparticles in cells by flow cytometry using light scatter and far‐red fluorescence , 2013, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[28]  Michael J Pencina,et al.  Carotid-wall intima-media thickness and cardiovascular events. , 2011, The New England journal of medicine.

[29]  R Cubeddu,et al.  A solid tissue phantom for photon migration studies. , 1997, Physics in medicine and biology.

[30]  D. Fixler,et al.  Correlation of magnetic AC field on cardiac myocyte Ca2+ transients at different magnetic DC levels , 2012, Bioelectromagnetics.

[31]  M. Rudelius,et al.  Neovascularization and angiogenic factors in advanced human carotid artery stenosis. , 2012, Circulation journal : official journal of the Japanese Circulation Society.

[32]  J. Narula,et al.  Advances in the understanding of plaque composition and treatment options: year in review. , 2014, Journal of the American College of Cardiology.

[33]  Dror Fixler,et al.  Subcutaneous gold nanoroad detection with diffusion reflection measurement , 2013, Journal of biomedical optics.

[34]  Sven Burgdorf,et al.  M2-like macrophages are responsible for collagen degradation through a mannose receptor–mediated pathway , 2013, The Journal of cell biology.

[35]  K. Toutouzas,et al.  Imaging of the vulnerable plaque: noninvasive and invasive techniques. , 2008, The American journal of the medical sciences.

[36]  Menachem Motiei,et al.  Gold nanorods as absorption contrast agents for the noninvasive detection of arterial vascular disorders based on diffusion reflection measurements. , 2014, Nano letters.

[37]  J. Turkevich,et al.  Coagulation of Colloidal Gold , 2002 .

[38]  Menachem Motiei,et al.  A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods , 2012, International journal of nanomedicine.

[39]  T. Yoon,et al.  Semi‐quantitative estimation of cellular SiO2 nanoparticles using flow cytometry combined with X‐ray fluorescence measurements , 2014, Cytometry. Part A : the journal of the International Society for Analytical Cytology.