Nanomedicine highlights in atherosclerosis

  • Varvara KaragkiozakiEmail author
Part of the following topical collections:
  1. Nanostructured Materials 2012. Special Issue Editors: Juan Manuel Rojo, Vasileios Koutsos


Atherosclerosis is a multifactorial disease and many different approaches have been attempted for its accurate diagnosis and treatment. The disease is induced by a low-grade inflammatory process in the vascular wall, leading through a cascade of events to the eventual formation of atheromatous plaque and arterial stenosis. Different types of cells participate in the process making more difficult to recognize the potential cellular targets within the plaques for their effective treatment. The rise of nanomedicine over the last decade has provided new types of drug delivery nanosystems that are able to be delivered to a specific diseased site of the vessel for imaging while simultaneously act as therapeutic agents. In this paper, a review of the recent advances in nanomedicine that has provided novel insights to the disease diagnosis and treatment will be given in line with different nanotechnology-based approaches to advance the cardiovascular stents. The main complications of bare metal stents such as restenosis and of drug-eluting stents which is the late stent thrombosis are analyzed to comprehend the demand for emerging therapeutic strategies based on nanotechnology.


Nanomedicine Atherosclerosis Nanoparticles Nanotheranostics Stents Drug delivery 



This work has been partially supported by the NanoCardio Project “Nanomedicine for Advanced, Bio-active/-mimetic materials for Cardiovascular Implants,” funded by GSRT Greece and European Commission. The author would like to acknowledge Prof. Stergios Logothetidis, the director of LTFN lab, Aristotle University of Thessaloniki, Greece and Dr. Silke Krol from Fondazione I.R.C.C.S. Istituto Neurologico, Carlo Besta, Milan, Italy, for their fruitful discussions and collaboration during NanoCardio Project.


  1. Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia M, McNeil SE (2009) Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev 61:428–437. doi: 10.1016/j.addr.2009.03.009 CrossRefGoogle Scholar
  2. Alfonso F (2009) Treatment of In-stent Restenosis—Past, Present and Future. Eur Cardiol 5:74–78Google Scholar
  3. Anderson TJ (1999) Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol 34:631–638. doi: 10.1016/S0735-1097(99)00259-4 CrossRefGoogle Scholar
  4. Antonov AS, Kolodgie FD, Munn DH, Gerrity RG (2004) Regulation of macrophage foam cell formation by αvβ3 integrin: potential role in human atherosclerosis. Am J Pathol 165:247–258. doi: 10.1016/S0002-9440(10)63293-2 CrossRefGoogle Scholar
  5. Arora HC, Jensen MP, Yuan Y, Wu AG, Vogt S, Paunesku T, Woloschak GE (2012) Nanocarriers enhance doxorubicin uptake in drug-resistant ovarian cancer cells. Cancer Res 72:769–778. doi: 10.1158/0008-5472.CAN-11-2890 CrossRefGoogle Scholar
  6. Babu RV, Mallikarjun V, Nikhat SR, Srikanth G, Theoharis S, Krueger U et al (2009) Targeting gene delivery to activated vascular endothelium using anti e/p-selectin antibody linked to PAMAM dendrimers. J Immunol Meth 343:79–90. doi: 10.1016/j.jim.2008.12.005 CrossRefGoogle Scholar
  7. Badimóna L, Vilahurb G, Padrób T (2009) Lipoproteins, platelets and atherothrombosis. Rev Esp Cardiol 62:1161–1178. doi: 10.1016/S1885-5857(09)73331-6 CrossRefGoogle Scholar
  8. Banquy X, Leclair G, Rabanel JM, Argaw A, Bouchard J-Fo, Hildgen P, Giasson S (2008) Selectins ligand decorated drug carriers for activated endothelial cell targeting. J Bioconjug Chem 19:2030–2039. doi: 10.1021/bc800257m CrossRefGoogle Scholar
  9. Bavry A, Kumbhani D, Helton T, Borek P, Mood G, Bhatt D (2006) Late Thrombosis of DES: A meta-analysis of randomized clinical trials. J Am Med 119: 1056–61. doi: 10.1016/j.amjmed.2006.01.023 Google Scholar
  10. Bhargava B, Reddy K, Karthikeyan G, Raju R, Mishra S, Singh S (2006) A novel paclitaxel-eluting porous carbon–carbon NP coated nonpolymeric cobalt–chromium stent: evaluation in a porcine model. J Cath Cardiovasc Interv 67:698–702. doi: 10.1002/ccd.20698 CrossRefGoogle Scholar
  11. Boekhorst BC, Tilborg GA, Strijkers GJ, Nicolay K (2012) Molecular MRI of inflammation in atherosclerosis. Curr Cardiovasc Imaging Rep 5:60–68. doi: 10.1007/s12410-011-9114-4 CrossRefGoogle Scholar
  12. Briley-Saebo KC, Johansson LO, Hustvedt SO, Haldorsen AG, Bjornerud A, Fayad ZA, Ahlstrom HK (2006) Clearance of iron oxide particles in rat liver—effect of hydrated particle size and coating material on liver metabolism. Invest Radiol 41:560–571. doi: 10.1097/01.rli.0000221321.90261.09 CrossRefGoogle Scholar
  13. Burtea C, Ballet S, Laurent S, Rousseaux O, Dencausse A, Gonzalez W et al (2012) Development of a magnetic resonance imaging protocol for the characterization of atherosclerotic plaque by using vascular cell adhesion molecule-1 and apoptosis-targeted ultrasmall superparamagnetic iron oxide derivatives. Arterioscler Thromb Vasc Biol 32:e36–e48. doi: 10.1161/ATVBAHA.112.245415 CrossRefGoogle Scholar
  14. Caruthers SD, Cyrus T, Winter PM, Wickline SA, Lanza GM M (2009) Anti-angiogenic perfluorocarbon nanoparticles for diagnosis and treatment of atherosclerosis. Nanomed Nanobiotechnol 3:11–23. doi: 10.1002/wnan.9 Google Scholar
  15. Casals E, Pfaller T, Duschl A, Oostingh GJ, Puntes V (2010) Time evolution of the nanoparticle protein corona. ACS Nano 4:3623–3632. doi: 10.1021/nn901372t CrossRefGoogle Scholar
  16. Caves JM, Chaikof EL (2006) The evolving impact of microfabrication and nanotechnology on stent design. J Vasc Surg 44:1363–1368. doi: 10.1016/j.jvs.2006.08.046 CrossRefGoogle Scholar
  17. Channon K (2002) Endothelium and pathogenesis of atherosclerosis. J Med 30:54-58. doi: Google Scholar
  18. Chaw CS, Chooi KW, Liu XM, Tan CW, Wang L, Yang YY (2004) Thermally responsive core-shell nanoparticles self-assembled from cholesteryl end-capped and grafted polyacrylamides: drug incorporation and in vitro release. Biomaterials 25:4297–4308. doi: 10.1016/j.biomaterials.2003.10.095 CrossRefGoogle Scholar
  19. Chen MS, John JM, Chew DP et al (2006) Bare metal stent restenosis is not a benign clinical entity. Am Heart J 151:1260. doi: 10.1016/j.ahj.2005.08.011 CrossRefGoogle Scholar
  20. Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A, Insin N, Bawendi MG, Semmler-Behnke M, Frangioni JV, Tsuda A (2010) Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotech 28:1300–1303. doi: 10.1038/nbt.1696 CrossRefGoogle Scholar
  21. Chono S, Tauchi Y, Morimoto K (2006) Influence of particle size on the distributions of liposomes to atherosclerotic lesions in mice. Drug Dev Ind Pharm 32:125–135. doi: 10.1080/03639040500390645 CrossRefGoogle Scholar
  22. Chorny M, Fishbein Yellen BB, Alferiev IS, Bakay M, Ganta S, Adamo R et al (2010) Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields. Proc Natl Acad Sci USA 107:8346–8351. doi: 10.1073/pnas.0909506107 CrossRefGoogle Scholar
  23. Colombo A, Iakovou I (2004) Drug-eluting stents: the new gold standard for percutaneous coronary revascularisation. Eur Heart J 25:895–897. doi: 10.1016/j.ehj.2004.03.023 CrossRefGoogle Scholar
  24. Cutlip DE, Chauhan MS, Baim DS et al (2002) Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 40:2082–2089. doi: 10.1016/S0735-1097(02)02597-4 CrossRefGoogle Scholar
  25. Cyrus T, Zhang H, Allen JS, Williams TA, Hu G, Caruthers SD, Wickline SA, Lanza GM (2008) Intramural delivery of rapamycin with alphavbeta3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury. Arterioscler Thromb Vasc Biol 28:820–826. doi: 10.1161/ATVBAHA.107.156281 CrossRefGoogle Scholar
  26. De Graaf J, Hak-Lemmers HL, Hectors MP, Demacker PN et al (1991) Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb Vasc Biol 11:298–306. doi: 10.1161/01.ATV.11.2.298 CrossRefGoogle Scholar
  27. Dejana E (2004) Endothelial cell-to-cell junctions: happy together. Nat Rev Mol Cell Biol 5:261–270. doi: :10.1038/nrm1357 CrossRefGoogle Scholar
  28. Dell’Orco D, Lundqvist M, Oslakovic C, Cedervall T, Linse S (2010) Modeling the time evolution of the nanoparticle-protein corona in a body fluid. PLoS ONE 5:e10949. doi: 10.1371/journal.pone.0010949 CrossRefGoogle Scholar
  29. Deosarkar SP, Malgor R, Fu J, Kohn LD, Hanes J, Goetz DJ (2008) Polymeric particles conjugated with a ligand to VCAM-1 exhibit selective avid and focal adhesion to sites of atherosclerosis. J Biotechnol Bioeng 101:400–752. doi: 10.1002/bit.21885 CrossRefGoogle Scholar
  30. Douglas JS (2012) Drug-Eluting Stent Restenosis. A Need for New Technology? J Am Coll Cardiol Interv 5:738–740. doi: 10.1016/j.jcin.2012.03.019 Google Scholar
  31. Ehrenberg MS, Friedman AE, Finkelstein JN, Oberdörster G, McGrath JL (2009) The influence of protein adsorption on nanoparticle association with cultured endothelial cells. Biomater 30:603–610. doi: 10.1016/j.biomaterials.2008.09.050 CrossRefGoogle Scholar
  32. Falk E (2006) Pathogenesis of atherosclerosis. J Am Coll Cardiol 47:7–12. doi: 10.1016/jjacc.2005.09.068 CrossRefGoogle Scholar
  33. Falk E, Prediman K, Shah PK, Fuster V (1995) Coronary plaque disruption. Circulation 92:657–671. doi: 10.1161/01.CIR.92.3.657 CrossRefGoogle Scholar
  34. Finn A, Nakazawa G, Ladich E, Kolodgie F, Virmani R (2008) Does underlying plaque morphology play a role in vessel healing after drug-eluting stent implantation? J Am Coll Cardiol Imaging 1:485–488. doi: 10.1016/j.jcmg.2008.04.007 Google Scholar
  35. Frias JC, Williams KJ, Fisher EA, Fayad ZA (2004) Recombinant HDL-like nanoparticles: a specific contrast agent for MRI of atherosclerotic plaques. J Am Chem Soc 126:16316-7. doi: 10.1021/ja044911a Google Scholar
  36. Fulmer T (2009) Disrupting atherosclerosis. SciBX 3:79. doi: 10.1038/scibx.2009.79 Google Scholar
  37. Garg S, Serruys P (2010) Coronary stents: current status. J Am Coll Cardiol 56:1–42. doi: 10.1016/j.jacc.2010.06.007 CrossRefGoogle Scholar
  38. Genders TS, Meijboom WB, Meijs MFL, Schuijf JD, Mollet NR, Weustink AC, Pugliese F, Bax JJ, Cramer MJ et al (2009) CT coronary angiography in patients suspected of having coronary artery disease: decision making from various perspectives in the face of uncertainty. Radiology 253:734–744. doi: 10.1148/radiol.2533090507 CrossRefGoogle Scholar
  39. Goonewardena SN (2012) Approaching the asymptote: obstacles and opportunities for nanomedicine in cardiovascular disease. Curr Atheroscler Rep 14:247–253. doi: 10.1007/s11883-012-0249-9 CrossRefGoogle Scholar
  40. Gupta AS (2011) Nanomedicine approaches in vascular disease: a review. J Nanomed 7: 763–779. doi: Google Scholar
  41. Hansson GK (2005) Mechanisms of disease inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695. doi: 10.1056/NEJMra043430 CrossRefGoogle Scholar
  42. Hara H, Nakamura M, Palmaz JC, Schwartz RS (2006) Role of stent design and coatings on restenosis and thrombosis. Adv Drug Deliv Rev 58:377–386. doi: 10.1016/j.addr.2006.01.022 CrossRefGoogle Scholar
  43. Hildebrandt N, Hermsdorf D, Signorell R, Schmitz SA, Diederichsena U (2007) Superparamagnetic iron oxide nanoparticles functionalized with peptides by electrostatic interactions. Arkivoc (v): 79–90. doi: 10.1039/B406193D
  44. Hoffmann R, Mintz GS (2000) Coronary in-stent restenosis—predictors, treatment and prevention. Eur Heart J 21:1739–1749. doi: 10.1053/euhj.2000.2153 CrossRefGoogle Scholar
  45. Hoshino A, Fujioka K, Oku T et al (2004) Physicochemical properties and cellular toxicity of nanocrystal quantum dots depend on their surface modification. Nano Lett 4:2163–3163. doi: 10.1021/nl048715d CrossRefGoogle Scholar
  46. Inoue T, Croce K, Morooka T, Sakuma M, Node K, Simon DI (2011) Vascular inflammation and repair. Implications for re-endothelialization, restenosis, and stent thrombosis. J Am Coll Cardiol 10:1057–1066. doi: 10.1016/j.jcin.2011.05.025 Google Scholar
  47. Jayagopal A, Russ P, Haselton F (2007) Surface engineering of quantum dots for in-vivo vascular imaging. J Bioconjug Chem 18:1424–1433. doi: 10.1021/bc070020r CrossRefGoogle Scholar
  48. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R (2006) Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 48: 193–202. doi: Google Scholar
  49. Joner M, Morimoto K, Kasukawa H, Steigerwald K, Merl S et al (2008) Site-specific targeting of nanoparticle prednisolone reduces in-stent restenosis in a rabbit model of established atheroma. Arterioscler Thromb Vasc Biol 28:1960–1966. doi: 10.1161/ATVBAHA.108.170662 CrossRefGoogle Scholar
  50. Joo J, Nam HY, Nam SH, Baek I, Park JS (2009) A novel deposition method of plga nanoparticles on coronary stents. Bull Korean Chem Soc 30:1085–1087CrossRefGoogle Scholar
  51. Kang HW, Josephson L, Petrovsky A, Weissleder R, Bogdanov A (2002) Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. Bioconjug Chem 13:122–127. doi: 10.1021/bc0155521 CrossRefGoogle Scholar
  52. Karagkiozaki V, Logothetidis S, Laskarakis A, Giannoglou G, Lousinian S (2008a) AFM study of the thrombogenicity of carbon-based coatings for cardiovascular applications. J Mater Sci Eng B 152:16–21. doi: 10.1016/j.mseb.2008.06.013 CrossRefGoogle Scholar
  53. Karagkiozaki V, Logothetidis S, Lousinian S, Giannoglou G (2008) Impact of surface electric properties of carbon-based thin films on platelets activation for nano-medical and nano-sensing applications. J Int Nanomed 3:461–469. doi:
  54. Karagkiozaki V, Logothetidis S, Kalfagiannis N, Lousinian S, Giannoglou G (2009) AFM probing platelets activation behavior on titanium nitride nanocoatings for biomedical applications. J Nanomed 5:64–72. doi: 10.1016/j.nano.2008.07.005 Google Scholar
  55. Karagkiozaki V, Logothetidis S, Kassavetis S, Giannoglou G (2010) Nanomedicine for the reduction of the thrombogenicity of stent coatings. Int J Nanomed 5:239–248. doi:  10.2147/IJN.S7596 Google Scholar
  56. Karagkiozaki V, Karagiannidis P, Kalfagiannis N, Kavatzikidou P, Patsalas P, Georgiou D, Logothetidis S (2012a) Novel nanostructured biomaterials: implications for coronary stent thrombosis. Int J Nanomed 7:6063–6076. doi: 10.2147/IJN.S34320 Google Scholar
  57. Karagkiozaki V, Vavoulidis E, Karagiannidis PG, Gioti M, Fatouros DG, Vizirianakis IS, Logothetidis S (2012b) Development of a nanoporous and multilayer drug-delivery platform for medical implants. Int J Nanomed 7: 5327–38. doi: Google Scholar
  58. Karagkiozaki V, Vavoulidis E, Logothetidis S (2012c) Nanomedicine pillars and monitoring nanobiointeractions. In: Logothetidis S (ed) Nanomedicine and nanobiotechnology, 1st edn. Springer-Verlag, Berlin Heidelberg, pp 27–52CrossRefGoogle Scholar
  59. Kawasaki E, Player A (2005) Nanotechnology, nanomedicine, and the development of new, effective therapies for cancer. Nanomedicine J 1:101–109. doi: 10.1016/j.nano.2005.03.002 Google Scholar
  60. Kolodgie FD, John M, Khurana C, Farb A, Wilson PS, Acampado E et al (2002) Sustained reduction of in-stent neointimal growth with the use of a novel systemic nanoparticle paclitaxel. Circulation 106:1195–1198. doi: 10.1161/01 CrossRefGoogle Scholar
  61. Kreylingn WG, Hirn S, Schleh C (2010) Nanoparticles in the lung. Nat Biotech 28:1275–1276. doi: 10.1038/nbt.1735 CrossRefGoogle Scholar
  62. Krol S (2012) Challenges in drug delivery to the brain: nature is against us. J Control Release 164:145–155. doi: 10.1016/j.jconrel.2012.04.044 CrossRefGoogle Scholar
  63. Lanza GM, Yu X, Winter PM, Abendschein DR, Karukstis KK, Scott MJ et al (2002) Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent: implications for rational therapy of restenosis. Circulation 106:2842–2847. doi: 10.1161/01.CIR.0000044020.27990.32 CrossRefGoogle Scholar
  64. Li W, Tutton S, Vu AT, Pierchala L et al (2005) First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel USPIO-based blood pool agent. J Magn Reson Imaging 21:46–52. doi: 10.1002/jmri.20235 CrossRefGoogle Scholar
  65. Li D, Patel AR, Klibanov AL, Kramer CM, Ruiz M et al (2010) Molecular imaging of atherosclerotic plaques targeted to oxidized LDL receptor LOX-1by SPECT/CT and magnetic resonance. J Circ Cardiovasc Imaging 3:464–472. doi: 10.1161/CIRCIMAGING.109.896654 CrossRefGoogle Scholar
  66. Liistro F, Colombo A (2001) Late acute thrombosis after paclitaxel eluting stent implantation. Heart 86:262–264. doi: 10.1136/heart.86.3.262 CrossRefGoogle Scholar
  67. Lipinski MJ, Amirbekian V, Frias JC, Aguinaldo JG, Mani V, Briley-Saebo KC, Fuster V, Fallon JT, Fisher EA, Fayad ZA (2006) MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor. Magn Reson Med 56:601–610. doi: 10.1002/mrm.20995 CrossRefGoogle Scholar
  68. Lipinski MJ, Frias JC, Amirbekian V, Briley-Saebo KC et al (2009) Macrophage-specific lipid-based nanoparticles improve mri detection and characterization of human atherosclerosis. J Am Coll Cardiol Cardiovasc Imaging 2:637–647. doi: 10.1016/j.jcmg.2008.08.009 CrossRefGoogle Scholar
  69. Litovsky S, Madjid M, Zarrabi A, Casscells W, Willerson JT, Naghavi M (2003) Superparamagnetic iron oxide-based method for quantifying recruitment of monocytes to mouse atherosclerotic lesions in vivo. Circulation 107:1545–1549. doi: 10.1161/01.CIR.0000055323.57885.88 CrossRefGoogle Scholar
  70. Liu SQ, Tong YW, Yang YY (2005) Incorporation and in vitro release of doxorubicin in thermally sensitive micelles made from poly(N-isopropylacrylamide co-N, N-dimethylacrylamide)-b-poly(d, l-lactide-coglycolide) with varying compositions. Biomaterials 26:5064–5074CrossRefGoogle Scholar
  71. Lobatto ME, Fayad ZA, Silvera S, Vucic E, Calcagno C, Mani V et al (2010) Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis. J Mol Pharm 7:2020–2029. doi: 10.1021/mp100309y CrossRefGoogle Scholar
  72. Lobatto ME, Fuster V, Fayad ZA, Mulder WJ (2011) Perspectives and opportunities for nanomedicine in the management of atherosclerosis. Nat Rev Drug Discov 10:835–852. doi: 10.1038/nrd3578 CrossRefGoogle Scholar
  73. Lockman PR, Koziara JM, Mumper RJ, Allen DD (2004) Nanoparticle surface charges alter blood-brain barrier integrity and permeability. J Drug Target 12:635-641. doi: 10.1080/10611860400015936 Google Scholar
  74. Logothetidis S (2012) Nanomedicine and nanobiotechnology. Springer, Berlin HeidelbergCrossRefGoogle Scholar
  75. Luscher TF, Steffel J, Eberli FR, Joner M, Nakazawa G, Tanner FC, Virmani R (2007) Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications. J Circ 115:1051–1058. doi: 10.1161/CIRCULATIONAHA.106.675934 CrossRefGoogle Scholar
  76. Maguire PD, McLaughlin JA, Okpalugo TIT, Papakonstantinou P, McAdams ET et al (2005) Mechanical stability, corrosion performance and bioresponse of amorphous DLC for medical stents and guidewires. J Diam Relat Mater 14:1277–1288. doi: 10.1016/j.diamond.2004.12.023 CrossRefGoogle Scholar
  77. Maiseyeu A, Mihai G, Roy S, Kherada N, Simonetti O, Sen C, Sun Q, Parthasarathy S, Rajagopalan S (2010) Detection of macrophages via paramagnetic vesicles incorporating oxidatively tailored cholesterol ester: an approach for atherosclerosis imaging. J Nanomed 5:1341–1356. doi: 10.2217/nnm.10.87 CrossRefGoogle Scholar
  78. Marambio-Jones C, Hoek E (2010) A review of the antibacterial effects of silver nanomaterials and potential implications for human health and the environment. J Nanopart Res 12:1531–1551. doi.  10.1007/s11051-010-9900-y Google Scholar
  79. McCarthy JR (2010) Multifunctional agents for concurrent imaging and therapy in cardiovascular disease. Adv Drug Deliv Rev 62:1023–30. doi: 10.1016/j.addr.2010.07.004 Google Scholar
  80. McCarthy JR, Korngold E, Weissleder R, Jaffer AF (2010) A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis. Small 6:2041–2049. doi: 10.1002/smll.201000596 CrossRefGoogle Scholar
  81. Mehran R, Dangas G, Abizaid AS S, Mintz GS, Lansky AJ, Satler LF et al (1999) Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. J Circ 100:1872–1878. doi: 10.1161/01.CIR.100.18.1872 CrossRefGoogle Scholar
  82. Minchin RF, Martin DJ (2010) Nanoparticles for molecular imaging—an overview. Endocrinology 151:474–481. doi: 10.1210/en.2009-1012 CrossRefGoogle Scholar
  83. Mishkel GJ, Moore AL, Markwell S et al (2007) Long-term outcomes after management of restenosis or thrombosis of drug-eluting stents. J Am Coll Cardiol 49:181–184. doi: 10.1016/j.jacc.2006.08.049 CrossRefGoogle Scholar
  84. Monopoli MP, Walczyk D, Campbell A, Elia G, Lynch I, Bombelli FB, Dawson KA (2011) Physical–chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. J Am Chem Soc 133:2525–2534. doi: 10.1021/ja107583h CrossRefGoogle Scholar
  85. Morris JB, Olzinski AR, Bernard RE, Aravindhan K, Mirabile RC, Boyce R et al (2008) p38 MAPK inhibition reduces aortic ultrasmall superparamagnetic iron oxide uptake in a mouse model of atherosclerosis: mRI assessment. Arterioscler Thromb Vasc Biol 28:265–271. doi: 10.1161/ATVBAHA.107.151175 CrossRefGoogle Scholar
  86. Mura S, Couvreur P (2012) Nanotheranostics for personalized medicine. Adv Drug Deliv Rev 64:1394–1416. doi: 10.1016/j.addr.2012.06.006 CrossRefGoogle Scholar
  87. Nahrendorf M, Jaffer FA, Kelly KA, Sosnovik DE, Aikawa E, Libby P, Weissleder R (2006) Non-invasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. J Circ 114:1504–1511. doi: 10.1161/CIRCULATIONAHA.106.646380 CrossRefGoogle Scholar
  88. Nakano K, Egashira K, Masuda S, Funakoshi K, Zhao G, Kimura S et al (2009) Formulation of nanoparticle-eluting stents by a cationic electrodeposition coating technology efficient nano-drug delivery via bioabsorbable polymeric nanoparticle-eluting stents in porcine coronary arteries. J Am Coll Cardiol Interv 2:277–283. doi: 10.1016/j.jcin.2008.08.023 Google Scholar
  89. Nakazawa G, Finn AV, Joner M, Ladich E et al (2008) Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study. J Circ 118:1138–1145. doi: 10.1161/CIRCULATIONAHA.107.762047 CrossRefGoogle Scholar
  90. O’Brien B, Carrolla W (2009) The evolution of cardiovascular stent materials and surfaces in response to clinical drivers: a review. Acta Biomater 5:945–958. doi: 10.1016/j.actbio.2008.11.012 CrossRefGoogle Scholar
  91. Pache J, Kastrati A, Mehilli J et al (2003) Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO-2) trial. J Am Coll Cardiol 41:1283–1288. doi: 10.1016/S0735-1097(03)00119-0 CrossRefGoogle Scholar
  92. Panyama J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55:329–347. doi: 10.1016/j.addr.2012.09.023 CrossRefGoogle Scholar
  93. Peters D, Kastantin M, Kotamraju VK, Karmali PP, Gujraty K, Tirrell M, Ruoslahti E (2009) Targeting atherosclerosis by using modular, multifunctional micelles. Proc Natl Acad Sci USA 106:9815–9819. doi: 10.1073/pnas.0903369106 Google Scholar
  94. Potineni A, Lynn DM, Langer R, Amiji MM (2003) Poly(ethylene oxide)-modified poly(b-amino ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery. J Control Release 86:223–234. doi: 10.1016/S0168-3659(02)00374-7 CrossRefGoogle Scholar
  95. Rizzo M, Berneis K (2006) Low-density lipoprotein size and cardiovascular risk assessment. QJM 99:1–14. doi: 10.1093/qjmed/hci154 CrossRefGoogle Scholar
  96. Salata O (2004) Applications of nanoparticles in biology and medicine. J Nanobiotech 2:1–6. doi: 10.1186/1477-3155-2-3 CrossRefGoogle Scholar
  97. Sanhai WR, Sakamoto JH, Canady R, Ferrari M (2008) Seven challenges for nanomedicine. Nat Nanotech 3:242–244. doi: 10.1038/nnano.2008.114 CrossRefGoogle Scholar
  98. Schmehl J, Harder C, Hans P, Wendel H, Claus D, Claussen C, Tepe G (2008) Silicon carbide coating of nitinol stents to increase antithrombogenic properties and reduce nickel release. J Card Revasc Med 9:255–262. doi: 10.1016/j.carrev.2008.03.004 CrossRefGoogle Scholar
  99. Sheridan P, Crossman D (2002) Critical review of unstable angina and non-ST elevation myocardial infarction. Postgrad Med J 78:717–726. doi: 10.1136/pmj.78.926.717 CrossRefGoogle Scholar
  100. Song CX, Labhasetwar V, Murphy H, Qu X, Humphrey WR, Shebuski RJ, Levy RJ (1997) Formulation and characterization of biodegradable nanoparticles for intravascular local drug delivery. J Control Release 43:197–212. doi: 10.1016/S0168-3659(96)01484-8 CrossRefGoogle Scholar
  101. Soppimath KS, Tan DCW, Yang YY (2005) pH-Triggered thermally responsive polymer core-shell nanoparticles for drug delivery. Adv Mater 17:318–323. doi: 10.1002/adma.200401057 CrossRefGoogle Scholar
  102. Sousa JE, Costa MA, Abizaid A et al (2003) Sirolimus-eluting stent for the treatment of in-stent restenosis: a quantitative coronary angiography and three-dimensional intravascular ultrasound study. J Circ 107:24–27. doi: 10.1161/01.CIR.0000047063.22006.41 CrossRefGoogle Scholar
  103. Southworth R, Kaneda M, Chen J, Zhang L, Zhang H, Yang X, et al (2009) Renal vascular inflammation induced by Western diet in ApoE-null mice quantified by 19F NMR of VCAM-1 targeted nanobeacons. Nanomedicine 5:359–367. doi: 10.1016/j.nano.2008.12.002 Google Scholar
  104. Stone G, Moses J, Ellis S, Schofer J, Dawkins K, Morice M, Colombo A et al (2007) Safety and efficacy of sirolimus and paclitaxel-eluting stents. J N Engl Med 356:998–1008. doi: 10.1056/NEJMoa067193 CrossRefGoogle Scholar
  105. Tang TY, Muller KH, Graves MJ, Li ZY, Walsh SR, Young V, Sadat U et al (2009a) Iron oxide particles for atheroma imaging. Arterioscler Thromb Vasc Biol 29:1001–1008. doi: 10.1161/ATVBAHA.108.165514 CrossRefGoogle Scholar
  106. Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, et al (2009b) The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. J Am Coll Cardiol 53:2039–50. doi: 10.1016/j.jacc.2009.03.018
  107. Tang J, Lobatto ME, Read JC, Mieszawska AJ, Fayad ZA, Mulder WJM (2012) Nanomedical theranostics in cardiovascular disease. J Curr Cardiovasc Imaging Rep 5:19–25. doi: 10.1007/s12410-011-9120-6 CrossRefGoogle Scholar
  108. Tassa C, Shaw SY, Weissleder R (2011) Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics and therapy. Acc Chem Res 44:842–852. doi: 10.1021/ar200084x CrossRefGoogle Scholar
  109. Tenzer S, Docter D, Rosfa S, Wlodarski A, Kuharev J, Rekik A, Knauer SK, Bantz C, Nawroth T, Bier C et al (2011) Nanoparticle size is a critical physicochemical determinant of the human blood plasma corona: a comprehensive quantitative proteomic analysis. ACS Nano 5:7155–7167. doi: 10.1021/nn201950e CrossRefGoogle Scholar
  110. Tong S, Hou S, Zheng Z, Zhou J, Bao G (2010) Coating optimization of superparamagnetic iron oxide nanoparticles for high T2 relaxivity. Nano Lett 10:4607–4613. doi: 10.1021/nl102623x CrossRefGoogle Scholar
  111. Trivedi RA, Mallawarachi C, Graves MJ, Horsley J et al (2006) Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages. Arterioscler Thromb Vasc Biol 26:1601–1606. doi: 10.1161/01.ATV.0000222920.59760.df CrossRefGoogle Scholar
  112. Tu C, Ng TS, Sohi HK, Palko HA et al (2011) Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques. Biomaterials 29:7209–7216. doi: 10.1016/j.biomaterials.2011.06.026 CrossRefGoogle Scholar
  113. Ungvari Z, Kaley G, De Cabo R, Sonntag WE, Csiszar A (2010) Mechanisms of vascular aging: new perspectives. J Gerontol A Biol Sci Med Sci 65A(10):1028–1041. doi: 10.1093/gerona/glq113 CrossRefGoogle Scholar
  114. Uwatoku T, Shimokawa H, Abe K, Matsumoto Y, Hattori T, Oi K et al (2003) Application of nanoparticle technology for the prevention of restenosis after balloon injury in rats. Circ Res 92:e62–e69. doi: 10.1161/01.RES.0000069021.56380.E2 CrossRefGoogle Scholar
  115. Van der Wal AC, Becker AE (1999) Atherosclerotic plaque rupture—pathologic basis of plaque stability and instability. Cardiovasc Res 41(2):334–344. doi: 10.1016/S0008-6363(98)00276-4 CrossRefGoogle Scholar
  116. Vizirianakis IS, Fatouros DG (2012) Personalized nanomedicine: paving the way to the practical clinical utility of genomics and nanotechnology advancements. Adv Drug Deliv Rev 64:1359–1362. doi: 10.1016/j.addr.2012.09.034 CrossRefGoogle Scholar
  117. Vroman L, Adams AL, Fischer GC, Munoz PC (1980) Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces. Blood 55:156–159Google Scholar
  118. Wang YX, Hussain SM, Krestin GP (2011) Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11:2319–2331. doi: 10.3978/j.issn.2223-4292.2011.08.03 CrossRefGoogle Scholar
  119. Watanabe T, Haraoka S, Shimokama T (1996) Inflammatory and immunological nature of atherosclerosis. Int J Cardiol 54:S51–S60. doi: 10.1016/S0167-5273(96)88773-0 CrossRefGoogle Scholar
  120. Wickline SA, Neubauer AM, Winter P, Caruthers S, Lanza G, Samuel A (2006) Applications of nanotechnology to atherosclerosis, thrombosis, and vascular biology. Arterioscler Thromb Vasc Biol 26:435–441. doi: 10.1161/01.ATV.0000201069.47550.8b CrossRefGoogle Scholar
  121. Winter PM, Caruthers SD, Kassner A et al (2003) Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel αvβ3 -targeted nanoparticle and 1.5 tesla magnetic resonance imaging. J Cancer Res 63:5838–5843Google Scholar
  122. Winter PM, Caruthers SD, Lanza GM, Wickline SA (2010) Quantitative cardiovascular magnetic resonance for molecular imaging. J Cardiovasc Magn Reson 12:62. doi: 10.1186/1532-429X-12-62 CrossRefGoogle Scholar
  123. Yancy AD, Olzinski AR, Hu TC, Lenhard SC, Aravindhan K, Gruver SM, Jacobs PM, Willette RN, Jucker BM (2005) Differential uptake of ferumoxtran-10 and ferumoxytol, ultrasmall superparamagnetic iron oxide contrast agents in rabbit: critical determinants of atherosclerotic plaque labeling. J Magn Reson Imaging 21:432–442. doi: 10.1002/jmri.20283 CrossRefGoogle Scholar
  124. Yang Y, Wang Y, Powell R, Chan P (2006) Polymeric core-shell nanoparticles for therapeutics. Clin Exp Pharmacol Physiol 33:557–562. doi: 10.1111/j.1440-1681.2006.04408.x CrossRefGoogle Scholar
  125. Yu MK, Park J, Jon S (2012) Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics 2:3–44. doi: 10.7150/thno.3463 CrossRefGoogle Scholar
  126. Zhang L, Webster T (2009) Nanotechnology and nanomaterials: promises for improved tissue regeneration. Nano Today 4:66–80. doi: 10.1016/j.nantod.2008.10.014 CrossRefGoogle Scholar
  127. Zweers MLT, Engbers GHM, Grijpma DW, Feijen J (2006) Release of anti-restenosis drugs from poly (ethylene oxide)-poly (dl-lactic-co-glycolic acid) nanoparticles. J Control Release 114: 317–324.

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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Nanomedicine Group, Laboratory for Thin Films-Nanosystems & Nanometrology (LTFN), Physics DepartmentAristotle University of ThessalonikiThessalonikiGreece

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