Cardiovascular therapy through nanotechnology - How far are we still from bedside?

European Journal of Nanomedicine

Volumn 6, Issue 2, 2014, Pages 63-87

  Cicha, Iwona ^b   Garlichs, Christoph D ^a   Alexiou, Christoph ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

cardiovascular diseases; cardiovascular drug delivery nanosystems; clinical trials; diagnostic nanoparticles; nanomedicine

Indexed keywords

DIAGNOSIS; DISEASE CONTROL; MEDICAL NANOTECHNOLOGY; NANOTECHNOLOGY; PATIENT TREATMENT;

APPLICATIONS OF NANOTECHNOLOGIES; CARDIO-VASCULAR DISEASE; CARDIOVASCULAR APPLICATIONS; CHARACTERIZATION METHODS; CLINICAL PRACTICES; CLINICAL TRIAL; MULTICOMPONENTS; NON-COMMUNICABLE DISEASE;

DISEASES;

NANOCARRIER; NANOPARTICLE;

ABDOMINAL AORTA ANEURYSM; ACUTE CORONARY SYNDROME; ATHEROSCLEROSIS; BLOOD CLOT LYSIS; BRAIN ISCHEMIA; CARDIAC IMAGING; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CELL THERAPY; CEREBROVASCULAR ACCIDENT; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HUMAN; IN-STENT RESTENOSIS; MOLECULAR IMAGING; NANOMEDICINE; NANOPROBE; NANOTECHNOLOGY; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCALE UP; THERAPY; THROMBOSIS; TISSUE ENGINEERING;

EID: 84902287275     PISSN: 16625986     EISSN: 1662596X     Source Type: Journal    
DOI: 10.1515/ejnm-2014-0001     Document Type: Review

References (169)

1. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380: 2095-128.
2. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2224-60.
3. Hahn MA, Singh AK, Sharma P, Brown SC, Moudgil BM. Nanoparticles as contrast agents for in-vivo bioimaging: current status and future perspectives. Anal Bioanal Chem 2011;399:3-27.
4. Nahrendorf M, Zhang H, Hembrador S, Panizzi P, Sosnovik DE, Aikawa E, et al. Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation 2008;117:379-87.
5. Wang T, Mancuso JJ, Sapozhnikova V, Dwelle J, Ma LL, Willsey B, et al. Dual-wavelength multifrequency photothermal wave imaging combined with optical coherence tomography for macrophage and lipid detection in atherosclerotic plaques using gold nanoparticles. J Biomed Opt 2012;17:036009.
6. Kelly KA, Allport JR, Tsourkas A, Shinde-Patil VR, Josephson L, Weissleder R. Detection of vascular adhesion molecule-1 expression using a novel multimodal nanoparticle. Circ Res 2005;96:327-36.
7. Nahrendorf M, Jaffer FA, Kelly KA, Sosnovik DE, Aikawa E, Libby P, et al. Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 2006;114:1504-11.
8. Reynolds PR, Larkman DJ, Haskard DO, Hajnal JV, Kennea NL, George AJ, et al. Detection of vascular expression of E-selectin in vivo with MR imaging. Radiology 2006;241:469-76.
9. Jacobin-Valat MJ, Deramchia K, Mornet S, Hagemeyer CE, Bonetto S, Robert R, et al. MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis. NMR Biomed 2011;24:413-24.
10. Cicha IL, Alexiou C, Garlichs CD. Nanomedicine in diagnostics and therapy of cardiovascular diseases: beyond atherosclerotic plaque imaging. Nanotechnol Rev 2013;2:449-72.
11. Oh J, Feldman MD, Kim J, Sanghi P, Do D, Mancuso JJ, et al. Detection of macrophages in atherosclerotic tissue using magnetic nanoparticles and differential phase optical coherence tomography. J Biomed Opt 2008;13:054006.
12. Korosoglou G, Weiss RG, Kedziorek DA, Walczak P, Gilson WD, Schar M, et al. Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using "positive contrast" magnetic resonance imaging. J Am Coll Cardiol 2008;52:483-91.
13. Morishige K, Kacher DF, Libby P, Josephson L, Ganz P, Weissleder R, et al. High-resolution magnetic resonance imaging enhanced with superparamagnetic nanoparticles measures macrophage burden in atherosclerosis. Circulation 2010;122:1707-15.
14. Sigovan M, Kaye E, Lancelot E, Corot C, Provost N, Majd Z, et al. Anti-inflammatory drug evaluation in ApoE-/- mice by ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging. Invest Radiol 2012;47:546-52.
15. te Boekhorst BC, Bovens SM, Nederhoff MG, van de Kolk KW, Cramer MJ, van Oosterhout MF, et al. Negative MR contrast caused by USPIO uptake in lymph nodes may lead to false positive observations with in vivo visualization of murine atherosclerotic plaque. Atherosclerosis 2010;210:122-9.
16. Hamzah J, Kotamraju VR, Seo JW, Agemy L, Fogal V, Mahakian LM, et al. Specific penetration and accumulation of a homing peptide within atherosclerotic plaques of apolipoprotein E-deficient mice. Proc Natl Acad Sci USA 2011;108:7154-9.
17. Uchida M, Kosuge H, Terashima M, Willits DA, Liepold LO, Young MJ, et al. Protein cage nanoparticles bearing the LyP-1 peptide for enhanced imaging of macrophage-rich vascular lesions. ACS Nano 2011;5:2493-502.
18. Lipinski MJ, Frias JC, Amirbekian V, Briley-Saebo KC, Mani V, Samber D, et al. Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis. JACC Cardiovasc Imaging 2009;2:637-47.
19. Dellinger A, Olson J, Link K, Vance S, Sandros MG, Yang J, et al. Functionalization of gadolinium metallofullerenes for detecting atherosclerotic plaque lesions by cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2013;15:7.
20. Tu C, Ng TS, Sohi HK, Palko HA, House A, Jacobs RE, et al. Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques. Biomaterials 2011;32:7209-16.
21. Frias JC, Williams KJ, Fisher EA, Fayad ZA. Recombinant HDL-like nanoparticles: a specific contrast agent for MRI of atherosclerotic plaques. J Am Chem Soc 2004;126:16316-7.
22. Chen W, Vucic E, Leupold E, Mulder WJ, Cormode DP, Briley-Saebo KC, et al. Incorporation of an apoE-derived lipopeptide in high-density lipoprotein MRI contrast agents for enhanced imaging of macrophages in atherosclerosis. Contrast Media Mol Imaging 2008;3:233-42.
23. Wen S, Liu DF, Liu Z, Harris S, Yao YY, Ding Q, et al. OxLDLtargeted iron oxide nanoparticles for in vivo MRI detection of perivascular carotid collar induced atherosclerotic lesions in ApoE-deficient mice. J Lipid Res 2012;53:829-38.
24. Burtea C, Ballet S, Laurent S, Rousseaux O, Dencausse A, Gonzalez W, et al. 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 2012;32:e36-48.
25. Smith BR, Heverhagen J, Knopp M, Schmalbrock P, Shapiro J, Shiomi M, et al. Localization to atherosclerotic plaque and biodistribution of biochemically derivatized superparamagnetic iron oxide nanoparticles (SPIONs) contrast particles for magnetic resonance imaging (MRI). Biomed Microdevices 2007;9:719-27.
26. van Tilborg GA, Vucic E, Strijkers GJ, Cormode DP, Mani V, Skajaa T, et al. Annexin A5-functionalized bimodal nanoparticles for MRI and fluorescence imaging of atherosclerotic plaques. Bioconjug Chem 2010;21:1794-803.
27. Winter PM, Morawski AM, Caruthers SD, Fuhrhop RW, Zhang H, Williams TA, et al. Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles. Circulation 2003;108:2270-4.
28. Somanath PR, Malinin NL, Byzova TV. Cooperation between integrin alphavbeta3 and VEGFR2 in angiogenesis. Angiogenesis 2009;12:177-85.
29. 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;64:369-76.
30. Flacke S, Fischer S, Scott MJ, Fuhrhop RJ, Allen JS, McLean M, et al. Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques. Circulation 2001;104:1280-5.
31. 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 USA 2009;106:9815-9.
32. Makowski MR, Forbes SC, Blume U, Warley A, Jansen CH, Schuster A, et al. In vivo assessment of intraplaque and endothelial fibrin in ApoE(-/-) mice by molecular MRI. Atherosclerosis 2012;222:43-9.
33. Thompson RW, Geraghty PJ, Lee JK. Abdominal aortic aneurysms: basic mechanisms and clinical implications. Curr Probl Surg 2002;39:110-230.
34. Yao Y, Wang Y, Zhang Y, Li Y, Sheng Z, Wen S, et al. In vivo imaging of macrophages during the early-stages of abdominal aortic aneurysm using high resolution MRI in ApoE mice. PLoS One 2012;7:e33523.
35. Klink A, Heynens J, Herranz B, Lobatto ME, Arias T, Sanders HM, et al. In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging. J Am Coll Cardiol 2011;58: 2522-30.
36. Kitagawa T, Kosuge H, Uchida M, Dua MM, Iida Y, Dalman RL, et al. RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease. Mol Imaging Biol 2012;14:315-24.
37. Rausch M, Sauter A, Frohlich J, Neubacher U, Radu EW, Rudin M. Dynamic patterns of USPIO enhancement can be observed in macrophages after ischemic brain damage. Magn Reson Med 2001;46:1018-22.
38. Rausch M, Baumann D, Neubacher U, Rudin M. In-vivo visualization of phagocytotic cells in rat brains after transient ischemia by USPIO. NMR Biomed 2002;15:278-83.
39. Kleinschnitz C, Bendszus M, Frank M, Solymosi L, Toyka KV, Stoll G. In vivo monitoring of macrophage infiltration in experimental ischemic brain lesions by magnetic resonance imaging. J Cereb Blood Flow Metab 2003;23:1356-61.
40. Schroeter M, Saleh A, Wiedermann D, Hoehn M, Jander S. Histochemical detection of ultrasmall superparamagnetic iron oxide (USPIO) contrast medium uptake in experimental brain ischemia. Magn Reson Med 2004;52:403-6.
41. Wiart M, Davoust N, Pialat JB, Desestret V, Moucharrafie S, Cho TH, et al. MRI monitoring of neuroinflammation in mouse focal ischemia. Stroke 2007;38:131-7.
42. Frechou M, Beray-Berthat V, Raynaud JS, Meriaux S, Gombert F, Lancelot E, et al. Detection of vascular cell adhesion molecule-1 expression with USPIO-enhanced molecular MRI in a mouse model of cerebral ischemia. Contrast Media Mol Imaging 2013;8:157-64.
43. Protti A, Dong X, Andia ME, Yu B, Dokukina K, Chaubey S, et al. Assessment of inflammation with a very small iron-oxide particle in a murine model of reperfused myocardial infarction. J Magn Reson Imaging 2014;39:598-608.
44. Yang Y, Yang Y, Yanasak N, Schumacher A, Hu TC. Temporal and noninvasive monitoring of inflammatory-cell infiltration to myocardial infarction sites using micrometer-sized iron oxide particles. Magn Reson Med 2010;63:33-40.
45. Jackson SP. Arterial thrombosis - insidious, unpredictable and deadly. Nat Med 2011;17:1423-36.
46. Dimarsico L, Cymet T. Pulmonary embolism - a state of the clot review. Compr Ther 2007;33:184-91.
47. Davie EW, Kulman JD. An overview of the structure and function of thrombin. Semin Thromb Hemost 2006;32(Suppl 1):3-15.
48. Lin KY, Kwong GA, Warren AD, Wood DK, Bhatia SN. Nanoparticles that sense thrombin activity as synthetic urinary biomarkers of thrombosis. ACS Nano 2013;7:9001-9.
49. Lenain N, Freund M, Leon C, Cazenave JP, Gachet C. Inhibition of localized thrombosis in P2Y1-deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonist. J Thromb Haemost 2003;1:1144-9.
50. Kim DE, Kim JY, Sun IC, Schellingerhout D, Lee SK, Ahn CH, et al. Hyperacute direct thrombus imaging using computed tomography and gold nanoparticles. Ann Neurol 2013;73:617-25.
51. Cowles CL, Zhu X. Dual signal amplification for bioassays using ion release from nanolabels and ion-activated enzyme kinetics. Analyst 2012;137:4815-21.
52. Ling Y, Pong T, Vassiliou CC, Huang PL, Cima MJ. Implantable magnetic relaxation sensors measure cumulative exposure to cardiac biomarkers. Nat Biotechnol 2011;29:273-7.
53. Marinescu M, Chauveau F, Durand A, Riou A, Cho TH, Dencausse A, et al. Monitoring therapeutic effects in experimental stroke by serial USPIO-enhanced MRI. Eur Radiol 2013;23:37-47.
54. Rahmer J, Antonelli A, Sfara C, Tiemann B, Gleich B, Magnani M, et al. Nanoparticle encapsulation in red blood cells enables blood-pool magnetic particle imaging hours after injection. Phys Med Biol 2013;58:3965-77.
55. Sharma A, Madhunapantula SV, Robertson GP. Toxicological considerations when creating nanoparticle-based drugs and drug delivery systems. Expert Opin Drug Metab Toxicol 2012;8:47-69.
56. Puri A, Loomis K, Smith B, Lee JH, Yavlovich A, Heldman E, et al. Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic. Crit Rev Ther Drug Carrier Syst 2009;26:523-80.
57. Balazs DA, Godbey W. Liposomes for use in gene delivery. J Drug Deliv 2011;2011:326-497.
58. Huwyler J, Drewe J, Krahenbuhl S. Tumor targeting using liposomal antineoplastic drugs. Int J Nanomedicine 2008;3:21-9.
59. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Preat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 2012;161:505-22.
60. Sun G, Mao JJ. Engineering dextran-based scaffolds for drug delivery and tissue repair. Nanomedicine (Lond) 2012;7: 1771-84.
61. Varshosaz J. Dextran conjugates in drug delivery. Expert Opin Drug Deliv 2012;9:509-23.
62. Menon JU, Jadeja P, Tambe P, Vu K, Yuan B, Nguyen KT. Nanomaterials for photo-based diagnostic and therapeutic applications. Theranostics 2013;3:152-66.
63. Wahajuddin, Arora S. Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers. Int J Nanomedicine 2012;7:3445-71.
64. Tassa C, Shaw SY, Weissleder R. Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy. Acc Chem Res 2011;44:842-52.
65. Janko C, Durr S, Munoz LE, Lyer S, Chaurio R, Tietze R, et al. Magnetic drug targeting reduces the chemotherapeutic burden on circulating leukocytes. Int J Mol Sci 2013;14:7341-55.
66. Lyer S, Tietze R, Jurgons R, Struffert T, Engelhorn T, Schreiber E, et al. Visualisation of tumour regression after local chemotherapy with magnetic nanoparticles - a pilot study. Anticancer Res 2010;30:1553-7.
67. Tietze R, Lyer S, Durr S, Struffert T, Engelhorn T, Schwarz M, et al. Efficient drug-delivery using magnetic nanoparticles - biodistribution and therapeutic effects in tumour bearing rabbits. Nanomedicine 2013;9:961-71.
68. Tietze R, Rahn H, Lyer S, Schreiber E, Mann J, Odenbach S, et al. Visualization of superparamagnetic nanoparticles in vascular tissue using XmuCT and histology. Histochem Cell Biol 2011;135:153-8.
69. Wang YX, Wang HH, Au DW, Zou BS, Teng LS. Pitfalls in employing superparamagnetic iron oxide particles for stem cell labelling and in vivo MRI tracking. Br J Radiol 2008;81:987-8.
70. Himes N, Min JY, Lee R, Brown C, Shea J, Huang X, et al. In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction. Magn Reson Med 2004;52:1214-9.
71. Sadek H, Latif S, Collins R, Garry MG, Garry DJ. Use of ferumoxides for stem cell labeling. Regen Med 2008;3:807-16.
72. Kim YJ, Huh YM, Choe KO, Choi BW, Choi EJ, Jang Y, et al. In vivo magnetic resonance imaging of injected mesenchymal stem cells in rat myocardial infarction; simultaneous cell tracking and left ventricular function measurement. Int J Cardiovasc Imaging 2009;25(Suppl 1):99-109.
73. Yao Y, Li Y, Ma G, Liu N, Ju S, Jin J, et al. In vivo magnetic resonance imaging of injected endothelial progenitor cells after myocardial infarction in rats. Mol Imaging Biol 2011;13:303-13.
74. Kim D, Chun BG, Kim YK, Lee YH, Park CS, Jeon I, et al. In vivo tracking of human mesenchymal stem cells in experimental stroke. Cell Transplant 2008;16:1007-12.
75. Song M, Kim Y, Kim Y, Ryu S, Song I, Kim SU, et al. MRI tracking of intravenously transplanted human neural stem cells in rat focal ischemia model. Neurosci Res 2009;64:235-9.
76. Lee ES, Chan J, Shuter B, Tan LG, Chong MS, Ramachandra DL, et al. Microgel iron oxide nanoparticles for tracking human fetal mesenchymal stem cells through magnetic resonance imaging. Stem Cells 2009;27:1921-31.
77. Guo RM, Cao N, Zhang F, Wang YR, Wen XH, Shen J, et al. Controllable labelling of stem cells with a novel superparamagnetic iron oxide-loaded cationic nanovesicle for MR imaging. Eur Radiol 2012;22:2328-37.
78. Wang Y, Xu F, Zhang C, Lei D, Tang Y, Xu H, et al. High MR sensitive fluorescent magnetite nanocluster for stem cell tracking in ischemic mouse brain. Nanomedicine 2011;7: 1009-19.
79. Zhang L, Wang Y, Tang Y, Jiao Z, Xie C, Zhang H, et al. High MRI performance fluorescent mesoporous silica-coated magnetic nanoparticles for tracking neural progenitor cells in an ischemic mouse model. Nanoscale 2013;5:4506-16.
80. Riegler J, Liew A, Hynes SO, Ortega D, O'Brien T, Day RM, et al. Superparamagnetic iron oxide nanoparticle targeting of MSCs in vascular injury. Biomaterials 2013;34:1987-94.
81. Takamiya M, Miyamoto Y, Yamashita T, Deguchi K, Ohta Y, Abe K. Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- and tissue plasminogen activatorrelated brain damages in mice. Neuroscience 2012;221:47-55.
82. Takamiya M, Miyamoto Y, Yamashita T, Deguchi K, Ohta Y, Ikeda Y, et al. Neurological and pathological improvements of cerebral infarction in mice with platinum nanoparticles. J Neurosci Res 2011;89:1125-33.
83. Yun X, Maximov VD, Yu J, Zhu H, Vertegel AA, Kindy MS. Nanoparticles for targeted delivery of antioxidant enzymes to the brain after cerebral ischemia and reperfusion injury. J Cereb Blood Flow Metab 2013;33:583-92.
84. Lu YM, Huang JY, Wang H, Lou XF, Liao MH, Hong LJ, et al. Targeted therapy of brain ischaemia using Fas ligand antibody conjugated PEG-lipid nanoparticles. Biomaterials 2014;35:530-7.
85. Miller DJ, Simpson JR, Silver B. Safety of thrombolysis in acute ischemic stroke: a review of complications, risk factors, and newer technologies. Neurohospitalist 2011;1:138-47.
86. Myerson J, He L, Lanza G, Tollefsen D, Wickline S. Thrombininhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis. J Thromb Haemost 2011;9:1292-300.
87. Palekar RU, Myerson JW, Schlesinger PH, Sadler JE, Pan H, Wickline SA. Thrombin-targeted liposomes establish a sustained localized anticlotting barrier against acute thrombosis. Mol Pharm 2013;10:4168-75.
88. Ma YH, Wu SY, Wu T, Chang YJ, Hua MY, Chen JP. Magnetically targeted thrombolysis with recombinant tissue plasminogen activator bound to polyacrylic acid-coated nanoparticles. Biomaterials 2009;30:3343-51.
89. Kawata H, Uesugi Y, Soeda T, Takemoto Y, Sung JH, Umaki K, et al. A new drug delivery system for intravenous coronary thrombolysis with thrombus targeting and stealth activity recoverable by ultrasound. J Am Coll Cardiol 2012;60:2550-7.
90. Korin N, Kanapathipillai M, Matthews BD, Crescente M, Brill A, Mammoto T, et al. Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science 2012;337: 738-42.
91. Paulis LE, Geelen T, Kuhlmann MT, Coolen BF, Schafers M, Nicolay K, et al. Distribution of lipid-based nanoparticles to infarcted myocardium with potential application for MRI-monitored drug delivery. J Control Release 2012;162: 276-85.
92. Binsalamah ZM, Paul A, Khan AA, Prakash S, Shum-Tim D. Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model. Int J Nanomedicine 2011;6:2667-78.
93. Chang MY, Yang YJ, Chang CH, Tang AC, Liao WY, Cheng FY, et al. Functionalized nanoparticles provide early cardioprotection after acute myocardial infarction. J Control Release 2013;170:287-94.
94. Zhang Y, Li W, Ou L, Wang W, Delyagina E, Lux C, et al. Targeted delivery of human VEGF gene via complexes of magnetic nanoparticle-adenoviral vectors enhanced cardiac regeneration. PLoS One 2012;7:e39490.
95. Liu J, Gu C, Cabigas EB, Pendergrass KD, Brown ME, Luo Y, et al. Functionalized dendrimer-based delivery of angiotensin type 1 receptor siRNA for preserving cardiac function following infarction. Biomaterials 2013;34:3729-36.
96. Katsuki S, Matoba T, Nakashiro S, Sato K, Koga JI, Nakano K, et al. Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque destabilization/rupture in mice by regulating the recruitment of inflammatory monocytes. Circulation 2014;129:896-906.
97. McCarthy JR, Korngold E, Weissleder R, Jaffer FA. A lightactivated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis. Small 2010;6:2041-9.
98. 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;26:2103-9.
99. Farb A, Sangiorgi G, Carter AJ, Walley VM, Edwards WD, Schwartz RS, et al. Pathology of acute and chronic coronary stenting in humans. Circulation 1999;99:44-52.
100. Schwartz RS, Chronos NA, Virmani R. Preclinical restenosis models and drug-eluting stents: still important, still much to learn. J Am Coll Cardiol 2004;44:1373-85.
101. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O'Shaughnessy C, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315-23.
102. Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, et al. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. J Am Med Assoc 2005;294:1215-23.
103. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 2006;48:193-202.
104. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. J Am Med Assoc 2005;293:2126-30.
105. Spertus JA, Kettelkamp R, Vance C, Decker C, Jones PG, Rumsfeld JS, et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation 2006;113:2803-9.
106. Joner M, Morimoto K, Kasukawa H, Steigerwald K, Merl S, Nakazawa G, et al. Site-specific targeting of nanoparticle prednisolone reduces in-stent restenosis in a rabbit model of established atheroma. Arterioscler Thromb Vasc Biol 2008;28:1960-6.
107. Tsukie N, Nakano K, Matoba T, Masuda S, Iwata E, Miyagawa M, et al. Pitavastatin-incorporated nanoparticle-eluting stents attenuate in-stent stenosis without delayed endothelial healing effects in a porcine coronary artery model. J Atheroscler Thromb 2013;20:32-45.
108. Masuda S, Nakano K, Funakoshi K, Zhao G, Meng W, Kimura S, et al. Imatinib mesylate-incorporated nanoparticle-eluting stent attenuates in-stent neointimal formation in porcine coronary arteries. J Atheroscler Thromb 2011;18:1043-53.
109. Polyak B, Fishbein I, Chorny M, Alferiev I, Williams D, Yellen B, et al. High field gradient targeting of magnetic nanoparticleloaded endothelial cells to the surfaces of steel stents. Proc Natl Acad Sci USA 2008;105:698-703.
110. Perea H, Aigner J, Heverhagen JT, Hopfner U, Wintermantel E. Vascular tissue engineering with magnetic nanoparticles: seeing deeper. J Tissue Eng Regen Med 2007;1:318-21.
111. Perea H, Aigner J, Hopfner U, Wintermantel E. Direct magnetic tubular cell seeding: a novel approach for vascular tissue engineering. Cells Tissues Organs 2006;183:156-65.
112. Ito A, Ino K, Hayashida M, Kobayashi T, Matsunuma H, Kagami H, et al. Novel methodology for fabrication of tissue-engineered tubular constructs using magnetite nanoparticles and magnetic force. Tissue Eng 2005;11:1553-61.
113. Gonzalez-Molina J, Riegler J, Southern P, Ortega D, Frangos CC, Angelopoulos Y, et al. Rapid magnetic cell delivery for large tubular bioengineered constructs. J R Soc Interface 2012;9:3008-16.
114. Akiyama H, Ito A, Sato M, Kawabe Y, Kamihira M. Construction of cardiac tissue rings using a magnetic tissue fabrication technique. Int J Mol Sci 2010;11:2910-20.
115. Schmitz SA, Taupitz M, Wagner S, Wolf KJ, Beyersdorff D, Hamm B. Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles. J Magn Reson Imaging 2001;14:355-61.
116. Trivedi RA, U-King-Im JM, Graves MJ, Kirkpatrick PJ, Gillard JH. Noninvasive imaging of carotid plaque inflammation. Neurology 2004;63:187-8.
117. 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;107:2453-8.
118. Trivedi RA, U-King-Im JM, Graves MJ, Cross JJ, Horsley J, Goddard MJ, et al. In vivo detection of macrophages in human carotid atheroma: temporal dependence of ultrasmall superparamagnetic particles of iron oxide-enhanced MRI. Stroke 2004;35:1631-5.
119. Trivedi RA, Mallawarachi C, U-King-Im JM, Graves MJ, Horsley J, Goddard MJ, et al. Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages. Arterioscler Thromb Vasc Biol 2006;26:1601-6.
120. Tang TY, Howarth SP, Miller SR, Graves MJ, U-King-Im JM, Trivedi RA, et al. Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques contralateral to symptomatic carotid stenosis: an ultra small superparamagnetic iron oxide enhanced magnetic resonance study. J Neurol Neurosurg Psychiatry 2007;78:1337-43.
121. Tang TY, Howarth SP, Miller SR, Graves MJ, U-King-Im JM, Li ZY, et al. Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: an ultrasmall superparamagnetic iron oxide enhanced magnetic resonance study. Eur J Vasc Endovasc Surg 2008;35:392-8.
122. Sadat U, Howarth SP, Usman A, Tang TY, Graves MJ, Gillard JH. Sequential imaging of asymptomatic carotid atheroma using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging: a feasibility study. J Stroke Cerebrovasc Dis 2013;22:e271-6.
123. Saleh A, Schroeter M, Jonkmanns C, Hartung HP, Modder U, Jander S. In vivo MRI of brain inflammation in human ischaemic stroke. Brain 2004;127(Pt 7):1670-7.
124. Saleh A, Schroeter M, Ringelstein A, Hartung HP, Siebler M, Modder U, et al. Iron oxide particle-enhanced MRI suggests variability of brain inflammation at early stages after ischemic stroke. Stroke 2007;38:2733-7.
125. Richards JM, Semple SI, MacGillivray TJ, Gray C, Langrish JP, Williams M, et al. Abdominal aortic aneurysm growth predicted by uptake of ultrasmall superparamagnetic particles of iron oxide: a pilot study. Circ Cardiovasc Imaging 2011;4:274-81.
126. Yilmaz A, Rosch S, Klingel K, Kandolf R, Helluy X, Hiller KH, et al. Magnetic resonance imaging (MRI) of inflamed myocardium using iron oxide nanoparticles in patients with acute myocardial infarction - preliminary results. Int J Cardiol 2013;163:175-82.
127. Yilmaz A, Dengler MA, van der Kuip H, Yildiz H, Rosch S, Klumpp S, et al. Imaging of myocardial infarction using ultrasmall superparamagnetic iron oxide nanoparticles: a human study using a multi-parametric cardiovascular magnetic resonance imaging approach. Eur Heart J 2013;34:462-75.
128. Alam SR, Shah AS, Richards J, Lang NN, Barnes G, Joshi N, et al. Ultrasmall superparamagnetic particles of iron oxide in patients with acute myocardial infarction: early clinical experience. Circ Cardiovasc Imaging 2012;5:559-65.
129. Wilson SR, Sabatine MS, Braunwald E, Sloan S, Murphy SA, Morrow DA. Detection of myocardial injury in patients with unstable angina using a novel nanoparticle cardiac troponin I assay: observations from the PROTECT-TIMI 30 Trial. Am Heart J 2009;158:386-91.
130. Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, UKing- Im JM, 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;53:2039-50.
131. Degnan AJ, Patterson AJ, Tang TY, Howarth SP, Gillard JH. Evaluation of ultrasmall superparamagnetic iron oxide-enhanced MRI of carotid atherosclerosis to assess risk of cerebrovascular and cardiovascular events: follow-up of the ATHEROMA trial. Cerebrovasc Dis 2012;34:169-73.
132. Richards JM, Shaw CA, Lang NN, Williams MC, Semple SI, MacGillivray TJ, et al. In vivo mononuclear cell tracking using superparamagnetic particles of iron oxide: feasibility and safety in humans. Circ Cardiovasc Imaging 2012;5:509-17.
133. Chu-fan L, Xing W, Xun H, Gui-fu W, Cheng-heng H, Zhi-min D. Protective effect of lipid microspheres 1 on myocardial injury following elective percutaneous coronary intervention in patients with angina pectoris: a pilot study. J Cardiovasc Med (Hagerstown) 2011;12:790-4.
134. 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;1:624-34.
135. Margolis J, McDonald J, Heuser R, Klinke P, Waksman R, Virmani R, et al. Systemic nanoparticle paclitaxel (nab-paclitaxel) for in-stent restenosis I (SNAPIST-I): a first-in-human safety and dose-finding study. Clin Cardiol 2007;30:165-70.
136. Tang TY, Muller KH, Graves MJ, Li ZY, Walsh SR, Young V, et al. Iron oxide particles for atheroma imaging. Arterioscler Thromb Vasc Biol 2009;29:1001-8.
137. Howarth SP, Tang TY, Trivedi R, Weerakkody R, U-King-Im JM, Gaunt ME, et al. Utility of USPIO-enhanced MR imaging to identify inflammation and the fibrous cap: a comparison of symptomatic and asymptomatic individuals. Eur J Radiol 2009;70:555-60.
138. Neuwelt EA, Hamilton BE, Varallyay CG, Rooney WR, Edelman RD, Jacobs PM, et al. Ultrasmall superparamagnetic iron oxides (USPIOs): a future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)? Kidney Int 2009;75:465-74.
139. Soenen SJ, De Cuyper M. Assessing iron oxide nanoparticle toxicity in vitro: current status and future prospects. Nanomedicine (Lond) 2010;5:1261-75.
140. Hasebroock KM, Serkova NJ. Toxicity of MRI and CT contrast agents. Expert Opin Drug Metab Toxicol 2009;5: 403-16.
141. Bernd H, De Kerviler E, Gaillard S, Bonnemain B. Safety and tolerability of ultrasmall superparamagnetic iron oxide contrast agent: comprehensive analysis of a clinical development program. Invest Radiol 2009;44:336-42.
142. Winer JL, Liu CY, Apuzzo ML. The use of nanoparticles as contrast media in neuroimaging: a statement on toxicity. World Neurosurg 2012;78:709-11.
143. Desai N. Challenges in development of nanoparticle-based therapeutics. AAPS J 2012;14:282-95.
144. Asharani PV, Lianwu Y, Gong Z, Valiyaveettil S. Comparison of the toxicity of silver, gold and platinum nanoparticles in developing zebrafish embryos. Nanotoxicology 2011;5: 43-54.
145. Bar-Ilan O, Albrecht RM, Fako VE, Furgeson DY. Toxicity assessments of multisized gold and silver nanoparticles in zebrafish embryos. Small 2009;5:1897-910.
146. Van der Linden P, Ickx BE. The effects of colloid solutions on hemostasis. Can J Anaesth 2006;53(6 Suppl):S30-9.
147. Disa JJ, Polvora VP, Pusic AL, Singh B, Cordeiro PG. Dextranrelated complications in head and neck microsurgery: do the benefits outweigh the risks? A prospective randomized analysis. Plast Reconstr Surg 2003;112:1534-9.
148. Bhatt AP, Neppalli VT, Kelley EA, Schlueter AJ, Thomas CP. Dextran removal by plasmapheresis in a kidney-pancreas transplant recipient with dextran 40-induced osmotic nephrosis. Am J Kidney Dis 2011;57:621-3.
149. Dokka S, Toledo D, Shi X, Castranova V, Rojanasakul Y. Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes. Pharm Res 2000;17:521-5.
150. Hall JB, Dobrovolskaia MA, Patri AK, McNeil SE. Characterization of nanoparticles for therapeutics. Nanomedicine (Lond) 2007;2:789-803.
151. Keene AM, Peters D, Rouse R, Stewart S, Rosen ET, Tyner KM. Tissue and cellular distribution of gold nanoparticles varies based on aggregation/ agglomeration status. Nanomedicine (Lond) 2012;7:199-209.
152. Oberdorster G. Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. J Intern Med 2010;267:89-105.
153. Owens DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 2006;307:93-102.
154. Kumar A, Dhawan A. Genotoxic and carcinogenic potential of engineered nanoparticles: an update. Arch Toxicol 2013;87:1883-900.
155. Zolnik BS, Gonzalez-Fernandez A, Sadrieh N, Dobrovolskaia MA. Nanoparticles and the immune system. Endocrinology 2010;151:458-65.
156. Aillon KL, Xie Y, El-Gendy N, Berkland CJ, Forrest ML. Effects of nanomaterial physicochemical properties on in vivo toxicity. Adv Drug Deliv Rev 2009;61:457-66.
157. Lv H, Zhang S, Wang B, Cui S, Yan J. Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release 2006;114:100-9.
158. Yamashita K, Yoshioka Y, Higashisaka K, Mimura K, Morishita Y, Nozaki M, et al. Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat Nanotechnol 2011;6:321-8.
159. Buyukhatipoglu K, Miller TA, Clyne AM. Flame synthesis and in vitro biocompatibility assessment of superparamagnetic iron oxide nanoparticles: cellular uptake, toxicity and proliferation studies. J Nanosci Nanotechnol 2009;9:6834-43.
160. Dobrovolskaia MA, Neun BW, Clogston JD, Grossman JH, McNeil SE. Choice of method for endotoxin detection depends on nanoformulation. Nanomedicine (Lond) 2013. Dec. 20 [Epub ahead of print].
161. Kucki M, Cavelius C, Kraegeloh A. Interference of silica nanoparticles with the traditional Limulus amebocyte lysate gel clot assay. Innate Immun 2014;20:327-36.
162. Grainger DW. Nanotoxicity assessment: all small talk? Adv Drug Deliv Rev 2009;61:419-21.
163. Zolnik BS, Sadrieh N. Regulatory perspective on the importance of ADME assessment of nanoscale material containing drugs. Adv Drug Deliv Rev 2009;61:422-7.
164. Wacker M. Nanocarriers for intravenous injection - the long hard road to the market. Int J Pharm 2013;457:50-62.
165. Mei L, Zhang Z, Zhao L, Huang L, Yang XL, Tang J, et al. Pharmaceutical nanotechnology for oral delivery of anticancer drugs. Adv Drug Deliv Rev 2013;65:880-90.
166. Xie X, Tao Q, Zou Y, Zhang F, Guo M, Wang Y, et al. PLGA nanoparticles improve the oral bioavailability of curcumin in rats: characterizations and mechanisms. J Agric Food Chem 2011;59:9280-9.
167. Shaikh J, Ankola DD, Beniwal V, Singh D, Kumar MN. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci 2009;37:223-30.
168. Paliwal R, Paliwal SR, Agrawal GP, Vyas SP. Biomimetic solid lipid nanoparticles for oral bioavailability enhancement of low molecular weight heparin and its lipid conjugates: in vitro and in vivo evaluation. Mol Pharm 2011;8:1314-21.
169. Jiao Y, Ubrich N, Marchand-Arvier M, Vigneron C, Hoffman M, Lecompte T, et al. In vitro and in vivo evaluation of oral heparin-loaded polymeric nanoparticles in rabbits. Circulation 2002;105:230-5.