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Multimodality nanotracers for cardiovascular applications

Nature Clinical Practice Cardiovascular Medicine volume 5, pages S103–S111 (2008)Cite this article

Abstract

Targeted imaging and therapeutics is becoming a field of prime importance in the study and treatment of cardiovascular disease; it promises to enable early diagnosis, promote improved understanding of pathology, and offer a way to improve therapeutic efficacy. Agents, particularly for cardiovascular disease, have been reported to permit the in vivo imaging, by multiple modalities, of macrophages, vascular targets such as vascular cell adhesion molecule 1, and markers for angiogenesis such as αvβ3 integrin. In this Article, we first discuss the general concept of multimodality nanoparticles and then focus in greater depth on their clinical application for molecular imaging and therapy. Lastly, several examples of cardiovascular applications are discussed, including combined imaging and therapy approaches.

Key Points

  • The field of targeted imaging and therapeutics by the use of nanoparticles is rapidly expanding and becoming of prime importance in the study and treatment of cardiovascular disease

  • The use of nanoparticles promises to facilitate early diagnosis and improve the understanding of the pathology of cardiovascular disease, and offers ways to increase therapeutic efficacy of treatments for cardiovascular conditions

  • Agents have been reported that enable the in vivo imaging of macrophages, vascular targets such as cell adhesion molecules, and markers for angiogenesis, by a variety of imaging modalities

  • Targeted nanotherapeutics is considered to be one of the most promising new methods of therapeutic intervention for cardiovascular disease

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Figure 1: Schematic depicting the typical features and build-up of multimodal nanoparticles and how a nanoparticle might be targeted and made biocompatible via surface modification.
Figure 2: Quantum dots may be used as the basis of multimodal molecular imaging probes.
Figure 3: Imaging of macrophages in models of atherosclerosis.
Figure 4: Targeted, dye-conjugated, cross-linked iron oxide particles produced negative contrast (image darkening) in an MRI study of atherosclerotic mice.

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References

  1. Choudhury RP et al. (2004) Molecular, cellular and functional imaging of atherothrombosis. Nat Rev Drug Discov 3: 913–925

    Article  CAS  Google Scholar 

  2. Jaffer FA et al. (2006) Molecular and cellular imaging of atherosclerosis: emerging applications. J Am Coll Cardiol 47: 1328–1338

    Article  CAS  Google Scholar 

  3. Weissleder R and Mahmood U (2001) Molecular imaging. Radiology 219: 316–333

    Article  CAS  Google Scholar 

  4. Mulder WJ et al. (2006) Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging. NMR Biomed 19: 142–164

    Article  CAS  Google Scholar 

  5. Mulder WJ et al. (2007) Magnetic and fluorescent nanoparticles for multimodality imaging. Nanomedicine 2: 307–324

    Article  CAS  Google Scholar 

  6. Frullano L and Meade TJ (2007) Multimodal MRI contrast agents. J Biol Inorg Chem 12: 939–949

    Article  CAS  Google Scholar 

  7. Mulder WJ et al. (2005) MR molecular imaging and fluorescence microscopy for identification of activated tumor endothelium using a bimodal lipidic nanoparticle. FASEB J 19: 2008–2010

    Article  CAS  Google Scholar 

  8. Josephson L et al. (2002) Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes. Bioconjug Chem 13: 554–560

    Article  CAS  Google Scholar 

  9. Moghimi SM et al. (2005) Nanomedicine: current status and future prospects. FASEB J 19: 311–330

    Article  CAS  Google Scholar 

  10. Midgley PA et al. (2007) Nanotomography in the chemical, biological and materials sciences. Chem Soc Rev 36: 1477–1494

    Article  CAS  Google Scholar 

  11. Wickline SA et al. (2006) Applications of nanotechnology to atherosclerosis, thrombosis, and vascular biology. Arterioscler Thromb Vasc Biol 26: 435–441

    Article  CAS  Google Scholar 

  12. Bangham AD et al. (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13: 238–252

    Article  CAS  Google Scholar 

  13. Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4: 145–160

    Article  CAS  Google Scholar 

  14. Aragnol D and Leserman LD (1986) Immune clearance of liposomes inhibited by an anti-Fc receptor antibody in vivo. Proc Natl Acad Sci USA 86: 2699–2703

    Article  Google Scholar 

  15. Allen TM and Hansen C (1991) Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim Biophys Acta 1068: 133–141

    Article  CAS  Google Scholar 

  16. Allen TM et al. (1991) Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim Biophys Acta 1066: 29–36

    Article  CAS  Google Scholar 

  17. Soo Choi H et al. (2007) Renal clearance of quantum dots. Nat Biotechnol 25: 1165–1170

    Article  Google Scholar 

  18. Liu Y et al. (2007) Nanomedicine for drug delivery and imaging: a promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles. Int J Cancer 120: 2527–2537

    Article  CAS  Google Scholar 

  19. Yih TC and Wei C (2005) Nanomedicine in cancer treatment. Nanomedicine 1: 191–192

    Article  CAS  Google Scholar 

  20. Sofou S (2007) Surface-active liposomes for targeted cancer therapy. Nanomedicine 2: 711–724

    Article  CAS  Google Scholar 

  21. Allen TM (2002) Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2: 750–763

    Article  CAS  Google Scholar 

  22. Bulte JW and Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17: 484–499

    Article  CAS  Google Scholar 

  23. Michalet X et al. (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307: 538–544

    Article  CAS  Google Scholar 

  24. Lanza GM et al. (2006) Nanomedicine opportunities for cardiovascular disease with perfluorocarbon nanoparticles. Nanomedicine 1: 321–329

    Article  CAS  Google Scholar 

  25. Romberg B et al. (2008) Sheddable coatings for long-circulating nanoparticles. Pharm Res 25: 55–71

    Article  CAS  Google Scholar 

  26. Rutten A and Prokop M (2007) Contrast agents in X-ray computed tomography and its applications in oncology. Anticancer Agents Med Chem 7: 307–316

    Article  CAS  Google Scholar 

  27. Kim D et al. (2007) Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging. J Am Chem Soc 129: 7661–7665

    Article  CAS  Google Scholar 

  28. Rabin O et al. (2006) An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater 5: 118–122

    Article  CAS  Google Scholar 

  29. Strijkers GJ et al. (2007) MRI contrast agents: current status and future perspectives. Anticancer Agents Med Chem 7: 291–305

    Article  CAS  Google Scholar 

  30. Morawski AM et al. (2005) Targeted contrast agents for magnetic resonance imaging and ultrasound. Curr Opin Biotechnol 16: 89–92

    Article  CAS  Google Scholar 

  31. Roby A et al. (2007) Enhanced in vivo antitumor efficacy of poorly soluble PDT agent, meso-tetraphenylporphine, in PEG-PE-based tumor-targeted immunomicelles. Cancer Biol Ther 6: 1136–1142

    Article  CAS  Google Scholar 

  32. Gulati M et al. (1998) Lipophilic drug derivatives in liposomes. Int J Pharm 165: 129–168

    Article  CAS  Google Scholar 

  33. Lanza GM 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

    Article  CAS  Google Scholar 

  34. Liu Y et al. (2007) Nanomedicine for drug delivery and imaging: a promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles. Int J Cancer 120: 2527–2537

    Article  CAS  Google Scholar 

  35. O'Neal DP et al. (2004) Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett 209: 171–176

    Article  CAS  Google Scholar 

  36. Hood JD et al. (2002) Tumor regression by targeted gene delivery to the neovasculature. Science 296: 2404–2407

    Article  CAS  Google Scholar 

  37. Mastrobattista E et al. (2002) Targeted liposomes for delivery of protein-based drugs into the cytoplasm of tumor cells. J Liposome Res 12: 57–65

    Article  CAS  Google Scholar 

  38. Mulder WJ et al. (2004) A liposomal system for contrast-enhanced magnetic resonance imaging of molecular targets. Bioconjug Chem 15: 799–806

    Article  CAS  Google Scholar 

  39. Kao CY et al. (2003) Long-residence-time nano-scale liposomal iohexol for X-ray-based blood pool imaging. Acad Radiol 10: 475–483

    Article  Google Scholar 

  40. Hamilton A et al. (2002) Left ventricular thrombus enhancement after intravenous injection of echogenic immunoliposomes: studies in a new experimental model. Circulation 105: 2772–2778

    Article  Google Scholar 

  41. Marik J et al. (2007) Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP). Nucl Med Biol 34: 165–171

    Article  CAS  Google Scholar 

  42. Harrington KJ et al. (2001) Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res 7: 243–254

    CAS  PubMed  Google Scholar 

  43. Torchilin VP (2007) Micellar nanocarriers: pharmaceutical perspectives. Pharm Res 24: 1–16

    Article  CAS  Google Scholar 

  44. Torchilin VP (2004) Targeted polymeric micelles for delivery of poorly soluble drugs. Cell Mol Life Sci 61: 2549–2559

    Article  CAS  Google Scholar 

  45. Fortina P et al. (2007) Applications of nanoparticles to diagnostics and therapeutics in colorectal cancer. Trends Biotechnol 25:145–152

    Article  CAS  Google Scholar 

  46. Vogl TJ et al. (1996) Magnetic resonance imaging of focal liver lesions: comparison of the superparamagnetic iron oxide resovist versus gadolinium-DTPA in the same patient. Invest Radiol 31: 696–708

    Article  CAS  Google Scholar 

  47. Mack MG et al. (2002) Superparamagnetic iron oxide-enhanced MR imaging of head and neck lymph nodes. Radiology 222: 239–244

    Article  Google Scholar 

  48. Tang T et al. (2006) Assessment of inflammatory burden contralateral to the symptomatic carotid stenosis using high-resolution ultrasmall, superparamagnetic iron oxide-enhanced MRI. Stroke 37: 2266–2270

    Article  CAS  Google Scholar 

  49. de Vries IJ et al. (2005) Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 23: 1407–1413

    Article  CAS  Google Scholar 

  50. McCarthy JR et al. (2007) Targeted delivery of multifunctional magnetic nanoparticles. Nanomedicine 2: 153–167

    Article  CAS  Google Scholar 

  51. Kircher MF et al. (2003) A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. Cancer Res 63: 8122–8125

    CAS  PubMed  Google Scholar 

  52. Jaffer FA et al. (2006) Cellular imaging of inflammation in atherosclerosis using magnetofluorescent nanomaterials. Mol Imaging 5: 85–92

    Article  Google Scholar 

  53. Nahrendorf M et al. (2006) Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 114: 1504–1511

    Article  CAS  Google Scholar 

  54. Mulder WJ et al. (2006) Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Lett 6: 1–6

    Article  CAS  Google Scholar 

  55. Frias JC et al. (2004) Recombinant HDL-like nanoparticles: a specific contrast agent for MRI of atherosclerotic plaques. J Am Chem Soc 126: 16316–16317

    Article  CAS  Google Scholar 

  56. Zheng G et al. (2005) 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

    Article  CAS  Google Scholar 

  57. Frias JC et al. (2006) Properties of a versatile nanoparticle platform contrast agent to image and characterize atherosclerotic plaques by magnetic resonance imaging. Nano Lett 6: 2220–2224

    Article  CAS  Google Scholar 

  58. Svenson S and Tomalia DA (2005) Dendrimers in biomedical applications—reflections on the field. Adv Drug Deliv Rev 57: 2106–2129

    Article  CAS  Google Scholar 

  59. Anderson EA et al. (2006) Viral nanoparticles donning a paramagnetic coat: conjugation of MRI contrast agents to the MS2 capsid. Nano Lett 6: 1160–1164

    Article  CAS  Google Scholar 

  60. Bridot JL et al. (2007) Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging. J Am Chem Soc 129: 5076–5084

    Article  CAS  Google Scholar 

  61. Rieter WJ et al. (2007) Hybrid silica nanoparticles for multimodal imaging. Angew Chem Int Ed Engl 46: 3680–3682

    Article  CAS  Google Scholar 

  62. Sitharaman B et al. (2005) Superparamagnetic gadonanotubes are high-performance MRI contrast agents. Chem Commun (Camb) 3915–3917

  63. Ruehm SG et al. (2001) Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits. Circulation 103: 415–422

    Article  CAS  Google Scholar 

  64. Kooi ME et al. (2003) 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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  67. Winter PM et al. (2006) Endothelial alpha(v)beta3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arterioscler Thromb Vasc Biol 26: 2103–2109

    Article  CAS  Google Scholar 

  68. Medarova Z et al. (2007) In vivo imaging of siRNA delivery and silencing in tumors. Nat Med 13: 372–377

    Article  CAS  Google Scholar 

  69. Pissuwan D et al. (2006) Therapeutic possibilities of plasmonically heated gold nanoparticles. Trends Biotechnol 24: 62–67

    Article  CAS  Google Scholar 

  70. Samia AC et al. (2003) Semiconductor quantum dots for photodynamic therapy. J Am Chem Soc 125: 15736–15737

    Article  CAS  Google Scholar 

  71. Roy I et al. (2005) Optical tracking of organically modified silica nanoparticles as DNA carriers: a nonviral, nanomedicine approach for gene delivery. Proc Natl Acad Sci USA 102: 279–284

    Article  CAS  Google Scholar 

  72. Ogawara K et al. (2006) Functional inhibition of NF-kappaB signal transduction in alphavbeta3 integrin expressing endothelial cells by using RGD-PEG-modified adenovirus with a mutant IkappaB gene. Arthritis Res Ther 8: R32

    Article  Google Scholar 

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Authors and Affiliations

  1. WJM Mulder is Assistant Professor of Radiology and Group Leader of the Nanomedicine Laboratory, DP Cormode is a Postdoctoral Fellow, and ZA Fayad is Director of the Translational and Molecular Imaging Institute, at Mount Sinai School of Medicine, New York, NY, USA,

    Willem JM Mulder, David P Cormode & Zahi A Fayad

  2. ME Lobatto is a Medical Student at the Leiden University Medical Center, Leiden, The Netherlands,

    Mark E Lobatto

  3. S Silvera is a Medical Doctor at the Radiology Department of Cochin Hospital in Paris, France,

    Stephane Silvera

  4. S Hak is Fellow in Biomedical NMR in the Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.,

    Sjoerd Hak

Authors
  1. Willem JM Mulder
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Correspondence to Willem JM Mulder.

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Mulder, W., Cormode, D., Hak, S. et al. Multimodality nanotracers for cardiovascular applications. Nat Rev Cardiol 5 (Suppl 2), S103–S111 (2008). https://doi.org/10.1038/ncpcardio1242

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