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  • Review Article
  • Published:

Perspectives and opportunities for nanomedicine in the management of atherosclerosis

An Erratum to this article was published on 31 October 2011

This article has been updated

Key Points

  • Nanomedicine — the use of nanotechnology for medical purposes — is a fast-growing field that has had numerous applications in cancer and is now increasingly being considered for atherosclerosis, the major cause of cardiovascular disease.

  • Several methods of targeting atherosclerotic plaques using nanoparticles have been explored, which can be classified into nonspecific targeting, specific targeting of the vasculature as well as specific targeting of plaque components either with synthetic nanoparticles or via interaction through a natural conduit.

  • Nanoparticle-facilitated therapeutics can potentially be applied to target the liver and change lipid levels systemically, or they can consist of direct injections of high-density lipoprotein nanoparticles to enhance the transport of cholesterol in plaques to the liver for excretion. Nanotherapy can also be used to intervene in specific atherosclerotic plaque processes by depleting monocyte recruitment or decreasing plaque inflammation and neovascularization.

  • Silencing of plaque inflammation after a clinical event — such as a myocardial infarction or stroke — using nanotherapy is a promising therapeutic paradigm as it may improve the effectiveness of subsequent (statin) therapy.

  • Medical imaging is increasingly being applied to assess atherosclerosis and to evaluate the effects of therapeutic interventions. It allows the direct and non-invasive visualization of plaque build-up and plaque characteristics in animal models as well as in patients.

  • Nanoparticle-enhanced diagnostics allow the molecular imaging of atherosclerotic plaques by several clinically available imaging modalities, including magnetic resonance imaging, computed tomography, positron emission tomography and ultrasound imaging. Multimodal nanoparticles have exhibited valuable roles in the evaluation and corroboration of targeting mechanisms.

Abstract

The use of nanotechnology for medical purposes — nanomedicine — has grown exponentially over the past few decades. This is exemplified by the US Food and Drug Administration's approval of several nanotherapies for various conditions, as well as the funding of nanomedical programmes worldwide. Although originally the domain of anticancer therapy, recent advances have illustrated the considerable potential of nanomedicine in the diagnosis and treatment of atherosclerosis. This Review elaborates on nanoparticle-targeting concepts in atherosclerotic disease, provides an overview of the use of nanomedicine in atherosclerosis, and discusses potential future applications and clinical benefits.

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Figure 1: Targeting principles in atherosclerotic plaques.
Figure 2: Applications of nanomedicine in the treatment of atherosclerotic disease.
Figure 3: Imaging-assisted evaluation of nanomedical treatments in atherosclerosis.
Figure 4: Imaging and nanomedicine in atherosclerosis.
Figure 5: Nanoparticle-enhanced (molecular) imaging of atherosclerosis.
Figure 6: Nanoparticle-enhanced multimodal imaging of atherosclerosis.

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Change history

  • 31 October 2011

    The following sentence was inadvertently duplicated on page 835: Subsequently, several other nanomedicinal therapeutics have been approved for clinical use, including an albumin-bound nanoparticle delivering paclitaxel for the treatment of breast cancer (Abraxane; Abraxis BioScience) and liposomal amphotericin B for the treat­ment of fungal infections (AmBisome; Astellas Pharma). This has been removed from this both the html and pdf versions.

References

  1. Moghimi, S. M., Hunter, A. C. & Murray, J. C. Nanomedicine: current status and future prospects. FASEB J. 19, 311–330 (2005).

    CAS  PubMed  Google Scholar 

  2. Wagner, V., Dullaart, A., Bock, A. K. & Zweck, A. The emerging nanomedicine landscape. Nature Biotech. 24, 1211–1217 (2006).

    CAS  Google Scholar 

  3. Kim, B. Y., Rutka, J. T. & Chan, W. C. Nanomedicine. N. Engl. J. Med. 363, 2434–2443 (2010).

    CAS  PubMed  Google Scholar 

  4. Nagarajan, R. & Hatton, T. A. (eds) Nanoparticles: Synthesis, Stabilization, Passivation, and Functionalization 2–14 (American Chemical Society, Washington DC, 2008).

    Google Scholar 

  5. Mulder, W. J. et al. Nanoparticulate assemblies of amphiphiles and diagnostically active materials for multimodality imaging. Acc. Chem. Res. 42, 904–914 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Mitragotri, S. & Lahann, J. Physical approaches to biomaterial design. Nature Mater. 8, 15–23 (2009). This is a detailed review about the influence of biomaterial design on the in vivo behaviour of the biomaterials.

    CAS  Google Scholar 

  7. Zhang, L. et al. Nanoparticles in medicine: therapeutic applications and developments. Clin. Pharmacol. Ther. 83, 761–769 (2008).

    CAS  PubMed  Google Scholar 

  8. Farokhzad, O. C. & Langer, R. Impact of nanotechnology on drug delivery. ACS Nano 3, 16–20 (2009).

    CAS  PubMed  Google Scholar 

  9. Davis, M. E., Chen, Z. G. & Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature Rev. Drug Discov. 7, 771–782 (2008).

    CAS  Google Scholar 

  10. Allen, T. M. Long-circulating (sterically stabilized) liposomes for targeted drug delivery. Trends Pharmacol. Sci. 15, 215–220 (1994).

    CAS  PubMed  Google Scholar 

  11. van Dalen, E. C., Michiels, E. M., Caron, H. N. & Kremer, L. C. Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Syst. Rev. CD005006 (2010).

  12. Terreno, E., Castelli, D. D., Viale, A. & Aime, S. Challenges for molecular magnetic resonance imaging. Chem. Rev. 110, 3019–3042 (2010).

    CAS  PubMed  Google Scholar 

  13. Yu, S. B. & Watson, A. D. Metal-based X-ray contrast media. Chem. Rev. 99, 2353–2378 (1999).

    CAS  PubMed  Google Scholar 

  14. Chen, K. & Conti, P. S. Target-specific delivery of peptide-based probes for PET imaging. Adv. Drug Deliv. Rev. 62, 1005–1022 (2010).

    CAS  PubMed  Google Scholar 

  15. Kobayashi, H., Ogawa, M., Alford, R., Choyke, P. L. & Urano, Y. New strategies for fluorescent probe design in medical diagnostic imaging. Chem. Rev. 110, 2620–2640 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Allen, T. M. & Cullis, P. R. Drug delivery systems: entering the mainstream. Science 303, 1818–1822 (2004).

    CAS  PubMed  Google Scholar 

  17. Ford, E. S. et al. Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N. Engl. J. Med. 356, 2388–2398 (2007).

    CAS  PubMed  Google Scholar 

  18. Roger, V. L. et al. Heart disease and stroke statistics —2011 update: a report from the American Heart Association. Circulation 123, e18–e209 (2011).

    PubMed  Google Scholar 

  19. Naghavi, M. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 108, 1664–1672 (2003).

    PubMed  Google Scholar 

  20. Falk, E. Pathogenesis of atherosclerosis. J. Am. Coll. Cardiol. 47, C7–C12 (2006). This is a comprehensive review on the pathogenesis of atherosclerosis.

    CAS  PubMed  Google Scholar 

  21. Chiu, J. J. & Chien, S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol. Rev. 91, 327–387 (2011).

    PubMed  Google Scholar 

  22. Tabas, I., Williams, K. J. & Boren, J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 116, 1832–1844 (2007).

    CAS  PubMed  Google Scholar 

  23. Tabas, I. Macrophage death and defective inflammation resolution in atherosclerosis. Nature Rev. Immunol. 10, 36–46 (2010).

    CAS  Google Scholar 

  24. Moreno, P. R., Purushothaman, K. R., Sirol, M., Levy, A. P. & Fuster, V. Neovascularization in human atherosclerosis. Circulation 113, 2245–2252 (2006).

    PubMed  Google Scholar 

  25. Moreno, P. R., Sanz, J. & Fuster, V. Promoting mechanisms of vascular health: circulating progenitor cells, angiogenesis, and reverse cholesterol transport. J. Am. Coll. Cardiol. 53, 2315–2323 (2009).

    CAS  PubMed  Google Scholar 

  26. Kolodgie, F. D. et al. Elimination of neoangiogenesis for plaque stabilization: is there a role for local drug therapy? J. Am. Coll. Cardiol. 49, 2093–2101 (2007).

    CAS  PubMed  Google Scholar 

  27. Libby, P. Inflammation in atherosclerosis. Nature 420, 868–874 (2002).

    CAS  PubMed  Google Scholar 

  28. Hansson, G. K. & Libby, P. The immune response in atherosclerosis: a double-edged sword. Nature Rev. Immunol. 6, 508–519 (2006).

    CAS  Google Scholar 

  29. Falk, E., Shah, P. K. & Fuster, V. Coronary plaque disruption. Circulation 92, 657–671 (1995).

    CAS  PubMed  Google Scholar 

  30. Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Mantovani, A., Allavena, P., Sica, A. & Balkwill, F. Cancer-related inflammation. Nature 454, 436–444 (2008).

    CAS  PubMed  Google Scholar 

  32. Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nature Rev. Cancer 5, 161–171 (2005).

    CAS  Google Scholar 

  33. Peer, D. et al. Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnol. 2, 751–760 (2007).

    CAS  Google Scholar 

  34. Matsumura, Y. & Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46, 6387–6392 (1986).

    CAS  PubMed  Google Scholar 

  35. Fang, J., Nakamura, H. & Maeda, H. The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv. Drug Deliv. Rev. 63, 136–151 (2011).

    CAS  PubMed  Google Scholar 

  36. Tarbell, J. M. Shear stress and the endothelial transport barrier. Cardiovasc. Res. 87, 320–330 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. van Bochove, G. S. et al. Contrast enhancement by differently sized paramagnetic MRI contrast agents in mice with two phenotypes of atherosclerotic plaque. Contrast Media Mol. Imaging 6, 35–45 (2011).

    CAS  PubMed  Google Scholar 

  38. Flogel, U. et al. In vivo monitoring of inflammation after cardiac and cerebral ischemia by fluorine magnetic resonance imaging. Circulation 118, 140–148 (2008).

    PubMed  PubMed Central  Google Scholar 

  39. Torchilin, V. P. Multifunctional nanocarriers. Adv. Drug Deliv. Rev. 58, 1532–1555 (2006).

    CAS  PubMed  Google Scholar 

  40. Hansson, G. K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 352, 1685–1695 (2005).

    CAS  PubMed  Google Scholar 

  41. Jiang, W., Kim, B. Y., Rutka, J. T. & Chan, W. C. Nanoparticle-mediated cellular response is size-dependent. Nature Nanotechnol. 3, 145–150 (2008).

    CAS  Google Scholar 

  42. O'Neil, C. P. et al. Extracellular matrix binding mixed micelles for drug delivery applications. J. Control Release 137, 146–151 (2009).

    CAS  PubMed  Google Scholar 

  43. Briley-Saebo, K. C. et al. Targeted iron oxide particles for in vivo magnetic resonance detection of atherosclerotic lesions with antibodies directed to oxidation-specific epitopes. J. Am. Coll. Cardiol. 57, 337–347 (2011).

    CAS  PubMed  Google Scholar 

  44. Kirpotin, D. B. et al. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 66, 6732–6740 (2006). This study demonstrates that ligand-directed targeting can increase cell internalization.

    CAS  PubMed  Google Scholar 

  45. Bartlett, D. W., Su, H., Hildebrandt, I. J., Weber, W. A. & Davis, M. E. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc. Natl Acad. Sci. USA 104, 15549–15554 (2007).

    CAS  PubMed  Google Scholar 

  46. Lanza, G. M. et al. Angiogenesis imaging with vascular-constrained particles: the why and how. Eur. J. Nucl. Med. Mol. Imaging 37 (Suppl. 1), 114–126 (2010).

    Google Scholar 

  47. Nahrendorf, M. et al. Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 114, 1504–1511 (2006). This is an example of a multimodal nanoparticle being used to detect plaque inflammation via target-specific imaging of adhesion molecules.

    CAS  PubMed  Google Scholar 

  48. Libby, P. The forgotten majority: unfinished business in cardiovascular risk reduction. J. Am. Coll. Cardiol. 46, 1225–1228 (2005).

    PubMed  Google Scholar 

  49. Miller, G. J. & Miller, N. E. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet 1, 16–19 (1975).

    CAS  PubMed  Google Scholar 

  50. Gordon, D. J. & Rifkind, B. M. High-density lipoprotein — the clinical implications of recent studies. N. Engl. J. Med. 321, 1311–1316 (1989).

    CAS  PubMed  Google Scholar 

  51. Navab, M., Reddy, S. T., Van Lenten, B. J. & Fogelman, A. M. HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nature Rev. Cardiol. 8, 222–232 (2011).

    CAS  Google Scholar 

  52. Khera, A. V. et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N. Engl. J. Med. 364, 127–135 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Briel, M. et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis. BMJ 338, b92 (2009).

    PubMed  PubMed Central  Google Scholar 

  54. Degoma, E. M. & Rader, D. J. Novel HDL-directed pharmacotherapeutic strategies. Nature Rev. Cardiol. 8, 266–277 (2011).

    CAS  Google Scholar 

  55. Badimon, J. J., Badimon, L., Galvez, A., Dische, R. & Fuster, V. High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits. Lab. Invest. 60, 455–461 (1989).

    CAS  PubMed  Google Scholar 

  56. Badimon, J. J., Badimon, L. & Fuster, V. Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit. J. Clin. Invest. 85, 1234–1241 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Shah, P. K. et al. Effects of recombinant apolipoprotein A-IMilano on aortic atherosclerosis in apolipoprotein E-deficient mice. Circulation 97, 780–785 (1998).

    CAS  PubMed  Google Scholar 

  58. Shah, P. K. et al. High-dose recombinant apolipoprotein A-IMilano mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein E-deficient mice. Potential implications for acute plaque stabilization. Circulation 103, 3047–3050 (2001).

    CAS  PubMed  Google Scholar 

  59. Chiesa, G. et al. Recombinant apolipoprotein A-IMilano infusion into rabbit carotid artery rapidly removes lipid from fatty streaks. Circ. Res. 90, 974–980 (2002).

    CAS  PubMed  Google Scholar 

  60. Ibanez, B. et al. Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-IMilano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis. J. Am. Coll. Cardiol. 51, 1104–1109 (2008).

    CAS  PubMed  Google Scholar 

  61. Kaul, S. et al. Rapid reversal of endothelial dysfunction in hypercholesterolemic apolipoprotein E-null mice by recombinant apolipoprotein A-IMilano-phospholipid complex. J. Am. Coll. Cardiol. 44, 1311–1319 (2004).

    CAS  PubMed  Google Scholar 

  62. Nissen, S. E. et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290, 2292–2300 (2003). This article presents the results of a clinical trial with infusions of reconstituted HDL that demonstrated regression of coronary atherosclerosis as measured by intravascular ultrasound imaging.

    CAS  PubMed  Google Scholar 

  63. Nicholls, S. J. et al. Relationship between atheroma regression and change in lumen size after infusion of apolipoprotein A-I Milano. J. Am. Coll. Cardiol. 47, 992–997 (2006).

    CAS  PubMed  Google Scholar 

  64. Bloedon, L. T. et al. Safety, pharmacokinetics, and pharmacodynamics of oral apoA-I mimetic peptide D-4F in high-risk cardiovascular patients. J. Lipid Res. 49, 1344–1352 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Navab, M. et al. Structure and function of HDL mimetics. Arterioscler. Thromb. Vasc. Biol. 30, 164–168 (2010).

    CAS  PubMed  Google Scholar 

  66. Vickers, K. C., Palmisano, B. T., Shoucri, B. M., Shamburek, R. D. & Remaley, A. T. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nature Cell Biol. 13, 423–433 (2011).

    CAS  PubMed  Google Scholar 

  67. Rensen, P. C. et al. Recombinant lipoproteins: lipoprotein-like lipid particles for drug targeting. Adv. Drug Deliv. Rev. 47, 251–276 (2001).

    CAS  PubMed  Google Scholar 

  68. Yang, M. et al. Efficient cytosolic delivery of siRNA using HDL-mimicking nanoparticles. Small 7, 568–573 (2011).

    CAS  PubMed  Google Scholar 

  69. McMahon, K. M. et al. Biomimetic high density lipoprotein nanoparticles for nucleic acid delivery. Nano Lett. 11, 1208–1214 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Skajaa, T. et al. High-density lipoprotein-based contrast agents for multimodal imaging of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 30, 169–176 (2010).

    CAS  PubMed  Google Scholar 

  71. Thaxton, C. S., Daniel, W. L., Giljohann, D. A., Thomas, A. D. & Mirkin, C. A. Templated spherical high density lipoprotein nanoparticles. J. Am. Chem. Soc. 131, 1384–1385 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Skajaa, T. et al. The biological properties of iron oxide core high-density lipoprotein in experimental atherosclerosis. Biomaterials 32, 206–213 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Zheng, G., Chen, J., Li, H. & Glickson, J. D. Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents. Proc. Natl Acad. Sci. USA 102, 17757–17762 (2005).

    CAS  PubMed  Google Scholar 

  74. Cannon, C. P., Steinberg, B. A., Murphy, S. A., Mega, J. L. & Braunwald, E. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J. Am. Coll. Cardiol. 48, 438–445 (2006).

    CAS  PubMed  Google Scholar 

  75. Armitage, J. et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 376, 1658–1669 (2010).

    PubMed  Google Scholar 

  76. Zimmermann, T. S. et al. RNAi-mediated gene silencing in non-human primates. Nature 441, 111–114 (2006). This study demonstrates the potential of systemic lipid-lowering by liposome-encapsulated siRNA.

    CAS  PubMed  Google Scholar 

  77. Semple, S. C. et al. Rational design of cationic lipids for siRNA delivery. Nature Biotech. 28, 172–176 (2010).

    CAS  Google Scholar 

  78. Love, K. T. et al. Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl Acad. Sci. USA 107, 1864–1869 (2010).

    CAS  PubMed  Google Scholar 

  79. Libby, P., Ridker, P. M. & Hansson, G. K. Inflammation in atherosclerosis: from pathophysiology to practice. J. Am. Coll. Cardiol. 54, 2129–2138 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Charo, I. F. & Taub, R. Anti-inflammatory therapeutics for the treatment of atherosclerosis. Nature Rev. Drug Discov. 10, 365–376 (2011).

    CAS  Google Scholar 

  81. Poon, M. et al. Dexamethasone inhibits macrophage accumulation after balloon arterial injury in cholesterol fed rabbits. Atherosclerosis 155, 371–380 (2001).

    CAS  PubMed  Google Scholar 

  82. Lobatto, M. E. et al. Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis. Mol. Pharm. 7, 2020–2029 (2010). This study shows the ability of non-invasive imaging to longitudinally monitor therapeutic response in a rabbit model of atherosclerosis after nanomedical treatment.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Mauriello, A. et al. Diffuse and active inflammation occurs in both vulnerable and stable plaques of the entire coronary tree: a histopathologic study of patients dying of acute myocardial infarction. J. Am. Coll. Cardiol. 45, 1585–1593 (2005).

    PubMed  Google Scholar 

  84. McCarthy, J. R., Korngold, E., Weissleder, R. & Jaffer, F. A. A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis. Small 6, 2041–2049 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Dangas, G. D. et al. In-stent restenosis in the drug-eluting stent era. J. Am. Coll. Cardiol. 56, 1897–1907 (2010).

    PubMed  Google Scholar 

  86. Pendyala, L. K. et al. The first-generation drug-eluting stents and coronary endothelial dysfunction. JACC Cardiovasc. Interv. 2, 1169–1177 (2009).

    PubMed  Google Scholar 

  87. Luscher, T. F. et al. Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications. Circulation 115, 1051–1058 (2007).

    PubMed  Google Scholar 

  88. Nakazawa, G. et al. The pathology of neoatherosclerosis in human coronary implants: bare-metal and drug-eluting stents. J. Am. Coll. Cardiol. 57, 1314–1322 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Danenberg, H. D. et al. Macrophage depletion by clodronate-containing liposomes reduces neointimal formation after balloon injury in rats and rabbits. Circulation 106, 599–605 (2002).

    CAS  PubMed  Google Scholar 

  90. Danenberg, H. D. et al. Liposomal alendronate inhibits systemic innate immunity and reduces in-stent neointimal hyperplasia in rabbits. Circulation 108, 2798–2804 (2003).

    CAS  PubMed  Google Scholar 

  91. Joner, M. et al. Site-specific targeting of nanoparticle prednisolone reduces in-stent restenosis in a rabbit model of established atheroma. Arterioscler. Thromb. Vasc. Biol. 28, 1960–1966 (2008).

    CAS  PubMed  Google Scholar 

  92. Ribichini, F. et al. Immunosuppressive therapy with oral prednisone to prevent restenosis after PCI. A multicenter randomized trial. Am. J. Med. 124, 434–443 (2011).

    CAS  PubMed  Google Scholar 

  93. Kolodgie, F. D. et al. Sustained reduction of in-stent neointimal growth with the use of a novel systemic nanoparticle paclitaxel. Circulation 106, 1195–1198 (2002).

    CAS  PubMed  Google Scholar 

  94. Uwatoku, T. et al. Application of nanoparticle technology for the prevention of restenosis after balloon injury in rats. Circ. Res. 92, e62–e69 (2003).

    CAS  PubMed  Google Scholar 

  95. Abid, M. R. et al. Forkhead transcription factors inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia. J. Biol. Chem. 280, 29864–29873 (2005).

    CAS  PubMed  Google Scholar 

  96. Li, J. M. et al. Local arterial nanoparticle delivery of siRNA for NOX2 knockdown to prevent restenosis in an atherosclerotic rat model. Gene Ther. 17, 1279–1287 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Lanza, G. M. et al. 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 (2002).

    CAS  PubMed  Google Scholar 

  98. Cyrus, T. et al. Intramural delivery of rapamycin with αvβ3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury. Arterioscler. Thromb. Vasc. Biol. 28, 820–826 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Chan, J. M. et al. Spatiotemporal controlled delivery of nanoparticles to injured vasculature. Proc. Natl Acad. Sci. USA 107, 2213–2218 (2010).

    CAS  PubMed  Google Scholar 

  100. Kaul, S. et al. Intramural delivery of recombinant apolipoprotein A-IMilano/phospholipid complex (ETC-216) inhibits in-stent stenosis in porcine coronary arteries. Circulation 107, 2551–2554 (2003).

    CAS  PubMed  Google Scholar 

  101. Nakano, K. et al. 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. JACC Cardiovasc. Interv. 2, 277–283 (2009).

    PubMed  Google Scholar 

  102. Polyak, B. et al. High field gradient targeting of magnetic nanoparticle-loaded endothelial cells to the surfaces of steel stents. Proc. Natl Acad. Sci. USA 105, 698–703 (2008).

    CAS  PubMed  Google Scholar 

  103. Chorny, M. et al. Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields. Proc. Natl Acad. Sci. USA 107, 8346–8351 (2010).

    CAS  PubMed  Google Scholar 

  104. Jain, R. K., Finn, A. V., Kolodgie, F. D., Gold, H. K. & Virmani, R. Antiangiogenic therapy for normalization of atherosclerotic plaque vasculature: a potential strategy for plaque stabilization. Nature Clin. Pract. Cardiovasc. Med. 4, 491–502 (2007).

    CAS  Google Scholar 

  105. Moulton, K. S. et al. Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 99, 1726–1732 (1999).

    CAS  PubMed  Google Scholar 

  106. Moulton, K. S. et al. Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc. Natl Acad. Sci. USA 100, 4736–4741 (2003).

    CAS  PubMed  Google Scholar 

  107. Winter, P. M. et al. Endothelial αvβ3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 26, 2103–2109 (2006). This was the first study to show the therapeutic potential of combined molecular imaging and drug delivery with targeted nanoparticles in a rabbit model of atherosclerosis.

    CAS  PubMed  Google Scholar 

  108. Winter, P. M. et al. Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis. JACC Cardiovasc. Imaging 1, 624–634 (2008).

    PubMed  PubMed Central  Google Scholar 

  109. Hedman, M. et al. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: Phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation 107, 2677–2683 (2003).

    CAS  PubMed  Google Scholar 

  110. Yla-Herttuala, S., Rissanen, T. T., Vajanto, I. & Hartikainen, J. Vascular endothelial growth factors: biology and current status of clinical applications in cardiovascular medicine. J. Am. Coll. Cardiol. 49, 1015–1026 (2007).

    PubMed  Google Scholar 

  111. Kim, J., Cao, L., Shvartsman, D., Silva, E. A. & Mooney, D. J. Targeted delivery of nanoparticles to ischemic muscle for imaging and therapeutic angiogenesis. Nano Lett. 11, 694–700 (2011).

    CAS  PubMed  Google Scholar 

  112. Celletti, F. L. et al. Vascular endothelial growth factor enhances atherosclerotic plaque progression. Nature Med. 7, 425–429 (2001).

    CAS  PubMed  Google Scholar 

  113. Peters, D. et al. Targeting atherosclerosis by using modular, multifunctional micelles. Proc. Natl Acad. Sci. USA 106, 9815–9819 (2009).

    CAS  PubMed  Google Scholar 

  114. Myerson, J., He, L., Lanza, G., Tollefsen, D. & Wickline, S. Thrombin-inhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis. J. Thromb. Haemost. 9, 1292–1300 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Uesugi, Y., Kawata, H., Jo, J., Saito, Y. & Tabata, Y. An ultrasound-responsive nano delivery system of tissue-type plasminogen activator for thrombolytic therapy. J. Control Release 147, 269–277 (2010).

    CAS  PubMed  Google Scholar 

  116. Sanz, J. & Fayad, Z. A. Imaging of atherosclerotic cardiovascular disease. Nature 451, 953–957 (2008). This is a review on the different methods of imaging atherosclerotic cardiovascular disease.

    CAS  PubMed  Google Scholar 

  117. Weissleder, R. & Mahmood, U. Molecular imaging. Radiology 219, 316–333 (2001).

    CAS  PubMed  Google Scholar 

  118. Chen, I. Y. & Wu, J. C. Cardiovascular molecular imaging: focus on clinical translation. Circulation 123, 425–443 (2011).

    PubMed  PubMed Central  Google Scholar 

  119. Leuschner, F. & Nahrendorf, M. Molecular imaging of coronary atherosclerosis and myocardial infarction: considerations for the bench and perspectives for the clinic. Circ. Res. 108, 593–606 (2011). This is a review on the processes that can be targeted to enable the detection of coronary atherosclerosis by molecular imaging.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Buono, C., Anzinger, J. J., Amar, M. & Kruth, H. S. Fluorescent pegylated nanoparticles demonstrate fluid-phase pinocytosis by macrophages in mouse atherosclerotic lesions. J. Clin. Invest. 119, 1373–1381 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Louie, A. Multimodality imaging probes: design and challenges. Chem. Rev. 110, 3146–3195 (2010). This is an extensive review on the synthesis and design of multimodal imaging probes.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Mulder, W. J. et al. Magnetic and fluorescent nanoparticles for multimodality imaging. Nanomedicine (Lond.) 2, 307–324 (2007).

    CAS  Google Scholar 

  123. Underhill, H. R., Hatsukami, T. S., Fayad, Z. A., Fuster, V. & Yuan, C. MRI of carotid atherosclerosis: clinical implications and future directions. Nature Rev. Cardiol. 7, 165–173 (2010).

    Google Scholar 

  124. Voros, S. et al. Coronary atherosclerosis imaging by Coronary CT angiography: current status, correlation with intravascular interrogation and meta-analysis. JACC Cardiovasc. Imaging 4, 537–548 (2011).

    PubMed  Google Scholar 

  125. Sirol, M. et al. Lipid-rich atherosclerotic plaques detected by gadofluorine-enhanced in vivo magnetic resonance imaging. Circulation 109, 2890–2896 (2004).

    CAS  PubMed  Google Scholar 

  126. Ruehm, S. G., Corot, C., Vogt, P., Kolb, S. & Debatin, J. F. Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits. Circulation 103, 415–422 (2001). This was the first study to use USPIO-enhanced MRI of atherosclerotic plaques in a rabbit model.

    CAS  PubMed  Google Scholar 

  127. Woollard, K. J. & Geissmann, F. Monocytes in atherosclerosis: subsets and functions. Nature Rev. Cardiol. 7, 77–86 (2010).

    Google Scholar 

  128. Kooi, M. E. et al. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation 107, 2453–2458 (2003).

    CAS  PubMed  Google Scholar 

  129. Tang, T. Y. et al. 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, 2039–2050 (2009).

    CAS  PubMed  Google Scholar 

  130. Fayad, Z. A., Razzouk, L., Briley-Saebo, K. C. & Mani, V. Iron oxide magnetic resonance imaging for atherosclerosis therapeutic evaluation: still “rusty?” J. Am. Coll. Cardiol. 53, 2051–2052 (2009).

    PubMed  PubMed Central  Google Scholar 

  131. Corti, R. et al. Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging. J. Am. Coll. Cardiol. 46, 106–112 (2005).

    CAS  PubMed  Google Scholar 

  132. Flacke, S. et al. Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques. Circulation 104, 1280–1285 (2001).

    CAS  PubMed  Google Scholar 

  133. Winter, P. M. et al. Molecular imaging of angiogenesis in early-stage atherosclerosis with αvβ3-integrin-targeted nanoparticles. Circulation 108, 2270–2274 (2003).

    CAS  PubMed  Google Scholar 

  134. Amirbekian, V. et al. Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. Proc. Natl Acad. Sci. USA 104, 961–966 (2007).

    CAS  PubMed  Google Scholar 

  135. van Tilborg, G. A. et al. Annexin A5-functionalized bimodal nanoparticles for MRI and fluorescence imaging of atherosclerotic plaques. Bioconjug. Chem. 21, 1794–1803 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Cormode, D. P. et al. Comparison of synthetic high density lipoprotein (HDL) contrast agents for MR imaging of atherosclerosis. Bioconjug. Chem. 20, 937–943 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Cormode, D. P. et al. Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform. Nano Lett. 8, 3715–3723 (2008). This paper reports the effect of including nanocrystals in the core of HDL to enable its detection by multiple imaging techniques without compromising the important biophysical features of HDL.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Skajaa, T. et al. Quantum dot and Cy5.5 labeled nanoparticles to investigate lipoprotein biointeractions via Förster resonance energy transfer. Nano Lett. 10, 5131–5138 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Torchilin, V. P., Frank-Kamenetsky, M. D. & Wolf, G. L. CT visualization of blood pool in rats by using long-circulating, iodine-containing micelles. Acad. Radiol. 6, 61–65 (1999).

    CAS  PubMed  Google Scholar 

  140. Rabin, O., Manuel Perez, J., Grimm, J., Wojtkiewicz, G. & Weissleder, R. An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nature Mater. 5, 118–122 (2006).

    CAS  Google Scholar 

  141. Hyafil, F. et al. Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography. Nature Med. 13, 636–641 (2007).

    CAS  PubMed  Google Scholar 

  142. Cormode, D. P. et al. Atherosclerotic plaque composition: analysis with multicolor CT and targeted gold nanoparticles. Radiology 256, 774–782 (2010).

    PubMed  PubMed Central  Google Scholar 

  143. Pan, D. et al. Computed tomography in color: NanoK-enhanced spectral CT molecular imaging. Angew. Chem. Int. Ed. Engl. 49, 9635–9639 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Rudd, J. H. et al. Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: ready for prime time? J. Am. Coll. Cardiol. 55, 2527–2535 (2010).

    PubMed  Google Scholar 

  145. Fujimoto, S. et al. Molecular imaging of matrix metalloproteinase in atherosclerotic lesions: resolution with dietary modification and statin therapy. J. Am. Coll. Cardiol. 52, 1847–1857 (2008).

    CAS  PubMed  Google Scholar 

  146. Rominger, A. et al. In vivo imaging of macrophage activity in the coronary arteries using 68Ga-DOTATATE PET/CT: correlation with coronary calcium burden and risk factors. J. Nucl. Med. 51, 193–197 (2010).

    PubMed  Google Scholar 

  147. Kietselaer, B. L. et al. Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis. N. Engl. J. Med. 350, 1472–1473 (2004).

    CAS  PubMed  Google Scholar 

  148. Nahrendorf, M. et al. Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation 117, 379–387 (2008). This study reports the effects of exploiting the favourable targeting properties of dextran-coated iron oxide nanoparticles for plaque imaging by PET–CT.

    CAS  PubMed  Google Scholar 

  149. Tassa, C., Shaw, S. Y. & Weissleder, R. Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy. Acc. Chem. Res. 10 Jun 2011 (doi:10.1021/ar200084x).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Almutairi, A. et al. Biodegradable dendritic positron-emitting nanoprobes for the noninvasive imaging of angiogenesis. Proc. Natl Acad. Sci. USA 106, 685–690 (2009).

    CAS  PubMed  Google Scholar 

  151. Nahrendorf, M. et al. Hybrid in vivo FMT-CT imaging of protease activity in atherosclerosis with customized nanosensors. Arterioscler. Thromb. Vasc. Biol. 29, 1444–1451 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Jaffer, F. A., Libby, P. & Weissleder, R. Optical and multimodality molecular imaging: insights into atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29, 1017–1024 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Wang, B. et al. Plasmonic intravascular photoacoustic imaging for detection of macrophages in atherosclerotic plaques. Nano Lett. 9, 2212–2217 (2009).

    CAS  PubMed  Google Scholar 

  154. Lanza, G. M. et al. A novel site-targeted ultrasonic contrast agent with broad biomedical application. Circulation 94, 3334–3340 (1996).

    CAS  PubMed  Google Scholar 

  155. Lindner, J. R. Molecular imaging of cardiovascular disease with contrast-enhanced ultrasonography. Nature Rev. Cardiol. 6, 475–481 (2009).

    CAS  Google Scholar 

  156. Rader, D. J. & Daugherty, A. Translating molecular discoveries into new therapies for atherosclerosis. Nature 451, 904–913 (2008).

    CAS  PubMed  Google Scholar 

  157. Dobrovolskaia, M. A. & McNeil, S. E. Immunological properties of engineered nanomaterials. Nature Nanotechnol. 2, 469–478 (2007). This review describes the immunotoxicological aspects of nanotechnology-based therapeutic or diagnostic nanoparticles.

    CAS  Google Scholar 

  158. Choi, H. S. & Frangioni, J. V. Nanoparticles for biomedical imaging: fundamentals of clinical translation. Mol. Imaging 9, 291–310 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Bentzon, J. F. & Falk, E. Atherosclerotic lesions in mouse and man: is it the same disease? Curr. Opin. Lipidol. 21, 434–440 (2010).

    CAS  PubMed  Google Scholar 

  160. Fitzgerald, K. T. et al. Standardization of models and methods used to assess nanoparticles in cardiovascular applications. Small 7, 705–717 (2011).

    CAS  PubMed  Google Scholar 

  161. Buxton, D. B. et al. Report of the national heart, lung, and blood institute working group on the translation of cardiovascular molecular imaging. Circulation 123, 2157–2163 (2011).

    PubMed  PubMed Central  Google Scholar 

  162. Libby, P., Ridker, P. M. & Hansson, G. K. Progress and challenges in translating the biology of atherosclerosis. Nature 473, 317–325 (2011). This review discusses targets for the treatment of atherosclerosis.

    CAS  PubMed  Google Scholar 

  163. Lindsay, A. C. & Choudhury, R. P. Form to function: current and future roles for atherosclerosis imaging in drug development. Nature Rev. Drug Discov. 7, 517–529 (2008). This review describes the role of atherosclerosis imaging on drug development.

    CAS  Google Scholar 

  164. Muntendam, P., McCall, C., Sanz, J., Falk, E. & Fuster, V. The BioImage Study: novel approaches to risk assessment in the primary prevention of atherosclerotic cardiovascular disease — study design and objectives. Am. Heart J. 160, 49–57 e1 (2010).

    PubMed  Google Scholar 

  165. Martinez, A. W. & Chaikof, E. L. Microfabrication and nanotechnology in stent design. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 3, 256–268 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Dvir, T., Timko, B. P., Kohane, D. S. & Langer, R. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnol. 6, 13–22 (2011).

    CAS  Google Scholar 

  167. Park, J. S. et al. A highly sensitive and selective diagnostic assay based on virus nanoparticles. Nature Nanotechnol. 4, 259–264 (2009).

    CAS  Google Scholar 

  168. Takahama, H. et al. Prolonged targeting of ischemic/reperfused myocardium by liposomal adenosine augments cardioprotection in rats. J. Am. Coll. Cardiol. 53, 709–717 (2009).

    CAS  PubMed  Google Scholar 

  169. Nahrendorf, M. et al. Detection of macrophages in aortic aneurysms by nanoparticle positron emission tomography–computed tomography. Arterioscler. Thromb. Vasc. Biol. 31, 750–757 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Lanza, G. M. et al. Rationale for a nanomedicine approach to thrombolytic therapy. Stroke 41, S42–S44 (2010).

    PubMed  PubMed Central  Google Scholar 

  171. Yu, L. et al. Autonomic denervation with magnetic nanoparticles. Circulation 122, 2653–2659 (2010).

    CAS  PubMed  Google Scholar 

  172. Choi, H. S. et al. Renal clearance of quantum dots. Nature Biotech. 25, 1165–1170 (2007). This is an excellent example of the influence of the size of a nanoparticle on its biodistribution and clearance.

    CAS  Google Scholar 

  173. Alexis, F., Pridgen, E., Molnar, L. K. & Farokhzad, O. C. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol. Pharm. 5, 505–515 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Klibanov, A. L., Maruyama, K., Torchilin, V. P. & Huang, L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 268, 235–237 (1990).

    CAS  PubMed  Google Scholar 

  175. Owens, D. E., & Peppas, N. A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 307, 93–102 (2006).

    CAS  PubMed  Google Scholar 

  176. Knop, K., Hoogenboom, R., Fischer, D. & Schubert, U. S. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew. Chem. Int. Ed. Engl. 49, 6288–6308 (2010).

    CAS  PubMed  Google Scholar 

  177. Petros, R. A. & DeSimone, J. M. Strategies in the design of nanoparticles for therapeutic applications. Nature Rev. Drug Discov. 9, 615–627 (2010). This is a review on recent advances in the design and therapeutic potential of nanoparticles.

    CAS  Google Scholar 

  178. Nel, A. E. et al. Understanding biophysicochemical interactions at the nano-bio interface. Nature Mater. 8, 543–557 (2009).

    CAS  Google Scholar 

  179. Torchilin, V. P. Recent advances with liposomes as pharmaceutical carriers. Nature Rev. Drug Discov. 4, 145–160 (2005).

    CAS  Google Scholar 

  180. Williams, K. J., Phillips, M. C. & Rodrigueza, W. V. Structural and metabolic consequences of liposome–lipoprotein interactions. Adv. Drug Deliv. Rev. 32, 31–43 (1998).

    CAS  PubMed  Google Scholar 

  181. Williams, K. J., Scalia, R., Mazany, K. D., Rodrigueza, W. V. & Lefer, A. M. Rapid restoration of normal endothelial functions in genetically hyperlipidemic mice by a synthetic mediator of reverse lipid transport. Arterioscler. Thromb. Vasc. Biol. 20, 1033–1039 (2000).

    CAS  PubMed  Google Scholar 

  182. Rodrigueza, W. V., Klimuk, S. K., Pritchard, P. H. & Hope, M. J. Cholesterol mobilization and regression of atheroma in cholesterol-fed rabbits induced by large unilamellar vesicles. Biochim. Biophys. Acta 1368, 306–320 (1998).

    CAS  PubMed  Google Scholar 

  183. Caride, V. J. & Zaret, B. L. Liposome accumulation in regions of experimental myocardial infarction. Science 198, 735–738 (1977).

    CAS  PubMed  Google Scholar 

  184. Hodis, H. N. et al. Relationship of arterial wall uptake of radiolabeled liposomes to the presence of monocyte/macrophage cells in the hypertensive and atherosclerotic arterial wall. Atherosclerosis 87, 109–117 (1991).

    CAS  PubMed  Google Scholar 

  185. Torchilin, V. P. et al. Targeted accumulation of polyethylene glycol-coated immunoliposomes in infarcted rabbit myocardium. FASEB J. 6, 2716–2719 (1992).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge D. P. Cormode for discussions and recommendations. Support for this work was partially provided by the International Atherosclerosis Society (M.E.L). This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) and the US National Institutes of Health (NIH), as a Program of Excellence in Nanotechnology (PEN) Award (Contract no. HHSN268201000045C), as well as by the NIH grants R01 EB009638 (Z.A.F.) and R01 CA155432 (W.J.M.M.).

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Glossary

Atherosclerosis

A chronic systemic inflammatory disease in which the arterial wall thickens as a result of the accumulation of fatty material within the vessel wall.

Drug-eluting stents

Stents that are typically coated with antiproliferative or immunosuppressive drugs for local release to prevent restenosis within the stent.

Apolipoprotein

The protein constituent of lipoproteins that provides cell specificity and is essential for their structural integrity.

Vasa vasorum

A microvascular network that supplies larger blood vessels with nutrients.

Stenosis

Luminal narrowing of a blood vessel.

Atherothrombotic events

Clinical events such as myocardial infarction or stroke that are the result of atherosclerotic plaque disruption with superimposed thrombosis.

Reverse cholesterol transport

Transport of cholesterol from peripheral cells to the liver for excretion.

Mononuclear phagocyte system

A branch of the immune system that consists of phagocytic cells that can remove macromolecules from circulation.

18F-FDG

A radioactive glucose analogue that is taken up by metabolically active cells, and is frequently used for molecular imaging in combination with positron emission tomography.

Restenosis

The reoccurence of stenosis after previous treatment.

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Lobatto, M., Fuster, V., Fayad, Z. et al. Perspectives and opportunities for nanomedicine in the management of atherosclerosis. Nat Rev Drug Discov 10, 835–852 (2011). https://doi.org/10.1038/nrd3578

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