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Published in: Current Cardiovascular Imaging Reports 1/2012

Open Access 01-02-2012 | Cardiac Molecular Imaging (F Jaffer, Section Editor)

Nanomedical Theranostics in Cardiovascular Disease

Authors: Jun Tang, Mark E. Lobatto, Joanna C. Read, Aneta J. Mieszawska, Zahi A. Fayad, Willem J. M. Mulder

Published in: Current Cardiovascular Imaging Reports | Issue 1/2012

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Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. New diagnostic and therapeutic strategies are needed to mitigate this public health issue. Advances in nanotechnology have generated innovative strategies for diagnosis and therapy in a variety of diseases, foremost in cancer. Based on these studies, a novel concept referred to as nanomedical theranostics, or the combinatory application of nanoparticulate agents to allow diagnostic therapy, is being explored to enable image-guided, personalized, or targeted treatment. Preclinically, theranostics have been gradually applied to CVD with several interesting and encouraging findings. This article summarizes studies and challenges of nanotheranostic strategies in CVD. It also evaluates nanotheranostic strategies that may potentially be utilized to benefit patients.
Literature
1.
go back to reference • Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM et al. Heart Disease and Stroke Statistics—2011 Update: A Report From the American Heart Association. Circulation.123(4):e18-e209. This article provides statistics of cardiovascular disease in the United States. • Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM et al. Heart Disease and Stroke Statistics—2011 Update: A Report From the American Heart Association. Circulation.123(4):e18-e209. This article provides statistics of cardiovascular disease in the United States.
2.
go back to reference Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005;46(7):1225–8.PubMedCrossRef Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005;46(7):1225–8.PubMedCrossRef
3.
go back to reference Libby P, DiCarli M, Weissleder R. The vascular biology of atherosclerosis and imaging targets. J Nucl Med. 2010;51 Suppl 1:33S–7S.PubMedCrossRef Libby P, DiCarli M, Weissleder R. The vascular biology of atherosclerosis and imaging targets. J Nucl Med. 2010;51 Suppl 1:33S–7S.PubMedCrossRef
4.
go back to reference • Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006;6(7):508–19. This article explains the pathophysiology of atherosclerosis. • Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006;6(7):508–19. This article explains the pathophysiology of atherosclerosis.
5.
go back to reference Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303(5665):1818–22.PubMedCrossRef Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303(5665):1818–22.PubMedCrossRef
6.
go back to reference Petros RA, DeSimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov. 2010;9(8):615–27.PubMedCrossRef Petros RA, DeSimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov. 2010;9(8):615–27.PubMedCrossRef
7.
go back to reference Moulton KS. Angiogenesis in atherosclerosis: gathering evidence beyond speculation. Curr Opin Lipidol. 2006;17(5):548–55.PubMedCrossRef Moulton KS. Angiogenesis in atherosclerosis: gathering evidence beyond speculation. Curr Opin Lipidol. 2006;17(5):548–55.PubMedCrossRef
8.
go back to reference Lanza GM, Winter PM, Caruthers SD, Hughes MS, Hu G, Schmieder AH, et al. Theragnostics for tumor and plaque angiogenesis with perfluorocarbon nanoemulsions. Angiogenesis. 2010;13(2):189–202.PubMedCrossRef Lanza GM, Winter PM, Caruthers SD, Hughes MS, Hu G, Schmieder AH, et al. Theragnostics for tumor and plaque angiogenesis with perfluorocarbon nanoemulsions. Angiogenesis. 2010;13(2):189–202.PubMedCrossRef
9.
go back to reference Mulder WJ, Cormode DP, Hak S, Lobatto ME, Silvera S, Fayad ZA. Multimodality nanotracers for cardiovascular applications. Nat Clin Pract Cardiovasc Med. 2008;5 Suppl 2:S103–11.PubMedCrossRef Mulder WJ, Cormode DP, Hak S, Lobatto ME, Silvera S, Fayad ZA. Multimodality nanotracers for cardiovascular applications. Nat Clin Pract Cardiovasc Med. 2008;5 Suppl 2:S103–11.PubMedCrossRef
10.
go back to reference Cormode DP, Skajaa T, van Schooneveld MM, Koole R, Jarzyna P, Lobatto ME, et al. Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform. Nano Lett. 2008;8(11):3715–23.PubMedCrossRef Cormode DP, Skajaa T, van Schooneveld MM, Koole R, Jarzyna P, Lobatto ME, et al. Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform. Nano Lett. 2008;8(11):3715–23.PubMedCrossRef
11.
go back to reference Janib SM, Moses AS, MacKay JA. Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliv Rev. 2010;62(11):1052–63.PubMedCrossRef Janib SM, Moses AS, MacKay JA. Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliv Rev. 2010;62(11):1052–63.PubMedCrossRef
12.
go back to reference Sanhai WR, Sakamoto JH, Canady R, Ferrari M. Seven challenges for nanomedicine. Nat Nanotechnol. 2008;3(5):242–4.PubMedCrossRef Sanhai WR, Sakamoto JH, Canady R, Ferrari M. Seven challenges for nanomedicine. Nat Nanotechnol. 2008;3(5):242–4.PubMedCrossRef
13.
go back to reference Kooi ME, Cappendijk VC, Cleutjens KB, Kessels AG, Kitslaar PJ, Borgers M, et al. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation. 2003;107(19):2453–8.PubMedCrossRef Kooi ME, Cappendijk VC, Cleutjens KB, Kessels AG, Kitslaar PJ, Borgers M, et al. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation. 2003;107(19):2453–8.PubMedCrossRef
14.
go back to reference Ruehm SG, Corot C, Vogt P, Kolb S, Debatin JF. Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits. Circulation. 2001;103(3):415–22.PubMed Ruehm SG, Corot C, Vogt P, Kolb S, Debatin JF. Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits. Circulation. 2001;103(3):415–22.PubMed
15.
go back to reference Morris JB, Olzinski AR, Bernard RE, Aravindhan K, Mirabile RC, Boyce R, et al. p38 MAPK inhibition reduces aortic ultrasmall superparamagnetic iron oxide uptake in a mouse model of atherosclerosis: MRI assessment. Arterioscler Thromb Vasc Biol. 2008;28(2):265–71.PubMedCrossRef Morris JB, Olzinski AR, Bernard RE, Aravindhan K, Mirabile RC, Boyce R, et al. p38 MAPK inhibition reduces aortic ultrasmall superparamagnetic iron oxide uptake in a mouse model of atherosclerosis: MRI assessment. Arterioscler Thromb Vasc Biol. 2008;28(2):265–71.PubMedCrossRef
16.
go back to reference • Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, JM UK-I 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. 2009;53(22):2039–50. This is the first clinical study that uses USPIO-enhanced MRI to evaluate therapeutic effects of high-dose statin treatment. • Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, JM UK-I 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. 2009;53(22):2039–50. This is the first clinical study that uses USPIO-enhanced MRI to evaluate therapeutic effects of high-dose statin treatment.
17.
go back to reference Weinberg MD, Lau JF, Rosenfield K, Olin JW. Peripheral artery disease. Part 2: medical and endovascular treatment. Nat Rev Cardiol. 2011;8(8):429–41.PubMedCrossRef Weinberg MD, Lau JF, Rosenfield K, Olin JW. Peripheral artery disease. Part 2: medical and endovascular treatment. Nat Rev Cardiol. 2011;8(8):429–41.PubMedCrossRef
18.
go back to reference Winter PM, Caruthers SD, Allen JS, Cai K, Williams TA, Lanza GM, et al. Molecular imaging of angiogenic therapy in peripheral vascular disease with alphanubeta3-integrin-targeted nanoparticles. Magn Reson Med. 2010;64(2):369–76.PubMed Winter PM, Caruthers SD, Allen JS, Cai K, Williams TA, Lanza GM, et al. Molecular imaging of angiogenic therapy in peripheral vascular disease with alphanubeta3-integrin-targeted nanoparticles. Magn Reson Med. 2010;64(2):369–76.PubMed
19.
go back to reference O’Brien B, Carroll W. The evolution of cardiovascular stent materials and surfaces in response to clinical drivers: a review. Acta Biomater. 2009;5(4):945–58.PubMedCrossRef O’Brien B, Carroll W. The evolution of cardiovascular stent materials and surfaces in response to clinical drivers: a review. Acta Biomater. 2009;5(4):945–58.PubMedCrossRef
20.
go back to reference Cyrus T, Zhang H, Allen JS, Williams TA, Hu G, Caruthers SD, et al. Intramural delivery of rapamycin with alphavbeta3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury. Arterioscler Thromb Vasc Biol. 2008;28(5):820–6.PubMedCrossRef Cyrus T, Zhang H, Allen JS, Williams TA, Hu G, Caruthers SD, et al. Intramural delivery of rapamycin with alphavbeta3-targeted paramagnetic nanoparticles inhibits stenosis after balloon injury. Arterioscler Thromb Vasc Biol. 2008;28(5):820–6.PubMedCrossRef
21.
go back to reference Chorny M, Fishbein I, Yellen BB, Alferiev IS, Bakay M, Ganta S, et al. Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields. Proc Natl Acad Sci U S A. 2010;107(18):8346–51.PubMedCrossRef Chorny M, Fishbein I, Yellen BB, Alferiev IS, Bakay M, Ganta S, et al. Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields. Proc Natl Acad Sci U S A. 2010;107(18):8346–51.PubMedCrossRef
22.
go back to reference Kim J, Cao L, Shvartsman D, Silva EA, Mooney DJ. Targeted delivery of nanoparticles to ischemic muscle for imaging and therapeutic angiogenesis. Nano Lett. 2011;11(2):694–700.PubMedCrossRef Kim J, Cao L, Shvartsman D, Silva EA, Mooney DJ. Targeted delivery of nanoparticles to ischemic muscle for imaging and therapeutic angiogenesis. Nano Lett. 2011;11(2):694–700.PubMedCrossRef
23.
go back to reference Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol. 2005;45(11):1775–80.PubMedCrossRef Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol. 2005;45(11):1775–80.PubMedCrossRef
24.
go back to reference Takahama H, Minamino T, Asanuma H, Fujita M, Asai T, Wakeno M, et al. Prolonged targeting of ischemic/reperfused myocardium by liposomal adenosine augments cardioprotection in rats. J Am Coll Cardiol. 2009;53(8):709–17.PubMedCrossRef Takahama H, Minamino T, Asanuma H, Fujita M, Asai T, Wakeno M, et al. Prolonged targeting of ischemic/reperfused myocardium by liposomal adenosine augments cardioprotection in rats. J Am Coll Cardiol. 2009;53(8):709–17.PubMedCrossRef
25.
go back to reference 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. 2011;9(7):1292–300.PubMedCrossRef 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. 2011;9(7):1292–300.PubMedCrossRef
26.
go back to reference Peters D, Kastantin M, Kotamraju VR, Karmali PP, Gujraty K, Tirrell M, et al. Targeting atherosclerosis by using modular, multifunctional micelles. Proc Natl Acad Sci U S A. 2009;106(24):9815–9.PubMedCrossRef Peters D, Kastantin M, Kotamraju VR, Karmali PP, Gujraty K, Tirrell M, et al. Targeting atherosclerosis by using modular, multifunctional micelles. Proc Natl Acad Sci U S A. 2009;106(24):9815–9.PubMedCrossRef
27.
go back to reference Jukema JW, Verschuren JJ, Ahmed TA, Quax PH. Restenosis after PCI. Part 1: pathophysiology and risk factors. Nat Rev Cardiol. Jukema JW, Verschuren JJ, Ahmed TA, Quax PH. Restenosis after PCI. Part 1: pathophysiology and risk factors. Nat Rev Cardiol.
28.
go back to reference Lanza GM, Yu X, Winter PM, Abendschein DR, Karukstis KK, Scott MJ, 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. 2002;106(22):2842–7.PubMedCrossRef Lanza GM, Yu X, Winter PM, Abendschein DR, Karukstis KK, Scott MJ, 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. 2002;106(22):2842–7.PubMedCrossRef
29.
go back to reference Winter PM, Neubauer AM, Caruthers SD, Harris TD, Robertson JD, Williams TA, et al. Endothelial alpha(v)beta3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arterioscler Thromb Vasc Biol. 2006;26(9):2103–9.PubMedCrossRef Winter PM, Neubauer AM, Caruthers SD, Harris TD, Robertson JD, Williams TA, et al. Endothelial alpha(v)beta3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arterioscler Thromb Vasc Biol. 2006;26(9):2103–9.PubMedCrossRef
30.
go back to reference Winter PM, Caruthers SD, Zhang H, Williams TA, Wickline SA, Lanza GM. Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis. JACC Cardiovasc Imaging. 2008;1(5):624–34.PubMedCrossRef Winter PM, Caruthers SD, Zhang H, Williams TA, Wickline SA, Lanza GM. Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis. JACC Cardiovasc Imaging. 2008;1(5):624–34.PubMedCrossRef
31.
go back to reference • Lobatto ME, Fayad ZA, Silvera S, Vucic E, Calcagno C, Mani V et al. Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis. Mol Pharm. 2010;7(6):2020–9. This study exemplifies that a theranostic approach can facilitate the development of nanotherapy. • Lobatto ME, Fayad ZA, Silvera S, Vucic E, Calcagno C, Mani V et al. Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis. Mol Pharm. 2010;7(6):2020–9. This study exemplifies that a theranostic approach can facilitate the development of nanotherapy.
32.
go back to reference McCarthy JR, Korngold E, Weissleder R, Jaffer FA. A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis. Small. 2010;6(18):2041–9.PubMedCrossRef McCarthy JR, Korngold E, Weissleder R, Jaffer FA. A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis. Small. 2010;6(18):2041–9.PubMedCrossRef
33.
go back to reference Fitzgerald KT, Holladay CA, McCarthy C, Power KA, Pandit A, Gallagher WM. Standardization of models and methods used to assess nanoparticles in cardiovascular applications. Small. 2011;7(6):705–17.PubMedCrossRef Fitzgerald KT, Holladay CA, McCarthy C, Power KA, Pandit A, Gallagher WM. Standardization of models and methods used to assess nanoparticles in cardiovascular applications. Small. 2011;7(6):705–17.PubMedCrossRef
34.
go back to reference Bentzon JF, Falk E. Atherosclerotic lesions in mouse and man: is it the same disease? Curr Opin Lipidol. 2010;21(5):434–40.PubMedCrossRef Bentzon JF, Falk E. Atherosclerotic lesions in mouse and man: is it the same disease? Curr Opin Lipidol. 2010;21(5):434–40.PubMedCrossRef
35.
go back to reference Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473(7347):317–25.PubMedCrossRef Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473(7347):317–25.PubMedCrossRef
36.
go back to reference Perazella MA. Current status of gadolinium toxicity in patients with kidney disease. Clin J Am Soc Nephrol. 2009;4(2):461–9.PubMedCrossRef Perazella MA. Current status of gadolinium toxicity in patients with kidney disease. Clin J Am Soc Nephrol. 2009;4(2):461–9.PubMedCrossRef
37.
go back to reference Chen J, Tung CH, Allport JR, Chen S, Weissleder R, Huang PL. Near-infrared fluorescent imaging of matrix metalloproteinase activity after myocardial infarction. Circulation. 2005;111(14):1800–5.PubMedCrossRef Chen J, Tung CH, Allport JR, Chen S, Weissleder R, Huang PL. Near-infrared fluorescent imaging of matrix metalloproteinase activity after myocardial infarction. Circulation. 2005;111(14):1800–5.PubMedCrossRef
38.
go back to reference Akinc A, Zumbuehl A, Goldberg M, Leshchiner ES, Busini V, Hossain N, et al. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nature Biotechnology. 2008;26(5):561–9.PubMedCrossRef Akinc A, Zumbuehl A, Goldberg M, Leshchiner ES, Busini V, Hossain N, et al. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nature Biotechnology. 2008;26(5):561–9.PubMedCrossRef
39.
go back to reference • Fayad ZA, Mani V, Woodward M, Kallend D, Abt M, Burgess T et al. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet. This is the first multicenter trial that uses noninvasive imaging to evaluate anti-atherosclerotic effects of a novel compound in patients. • Fayad ZA, Mani V, Woodward M, Kallend D, Abt M, Burgess T et al. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet. This is the first multicenter trial that uses noninvasive imaging to evaluate anti-atherosclerotic effects of a novel compound in patients.
Metadata
Title
Nanomedical Theranostics in Cardiovascular Disease
Authors
Jun Tang
Mark E. Lobatto
Joanna C. Read
Aneta J. Mieszawska
Zahi A. Fayad
Willem J. M. Mulder
Publication date
01-02-2012
Publisher
Current Science Inc.
Published in
Current Cardiovascular Imaging Reports / Issue 1/2012
Print ISSN: 1941-9066
Electronic ISSN: 1941-9074
DOI
https://doi.org/10.1007/s12410-011-9120-6

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