Fluorescence imaging of macrophages in atherosclerotic plaques using plasmonic gold nanorose

Macrophages are one of the most important cell types involved in the progression of atherosclerosis which can lead to myocardial infarction. To detect macrophages in atherosclerotic plaques, plasmonic gold nanorose is introduced as a nontoxic contrast agent for fluorescence imaging. We report macrophage cell culture and ex vivo tissue studies to visualize macrophages targeted by nanorose using scanning confocal microscopy. Atherosclerotic lesions were created in the aorta of a New Zealand white rabbit model subjected to a high cholesterol diet and double balloon injury. The rabbit was injected with nanoroses coated with dextran. A HeNe laser at 633 nm was used as an excitation light source and a acousto-optical beam splitter was utilized to collect fluorescence emission in 650-760 nm spectral range. Results of scanning confocal microscopy of macrophage cell culture and ex vivo tissue showed that nanoroses produce a strong fluorescence signal. The presence of nanorose in ex vivo tissue was further confirmed by photothermal wave imaging. These results suggest that scanning confocal microscopy can identify the presence and location of nanorose-loaded macrophages in atherosclerotic plaques.

[1]  V. Fuster,et al.  Coronary plaque disruption. , 1995, Circulation.

[2]  P. Libby,et al.  Stabilization of atherosclerotic plaques: New mechanisms and clinical targets , 2002, Nature Medicine.

[3]  Renu Virmani,et al.  Pathology of the thin-cap fibroatheroma: a type of vulnerable plaque. , 2003, Journal of interventional cardiology.

[4]  R. Webb,et al.  In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. , 1999, The Journal of investigative dermatology.

[5]  R. Virmani,et al.  Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[6]  François Mach,et al.  Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo , 1999, The Journal of experimental medicine.

[7]  R. Webb,et al.  In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. , 1995, The Journal of investigative dermatology.

[8]  M. Davies,et al.  Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. , 1993, British heart journal.

[9]  E Falk,et al.  Techniques characterizing the coronary atherosclerotic plaque: influence on clinical decision making? , 2000, Journal of the American College of Cardiology.

[10]  Marc D Feldman,et al.  Small multifunctional nanoclusters (nanoroses) for targeted cellular imaging and therapy. , 2009, ACS nano.

[11]  Thomas E. Milner,et al.  Nanorose and lipid detection in atherosclerotic plaque using dual-wavelength photothermal wave imaging , 2010, BiOS.

[12]  P. Libby,et al.  Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. , 1995, Proceedings of the National Academy of Sciences of the United States of America.