Calcium-Binding Nanoparticles for Vascular Disease

Abstract

Cardiovascular disease (CVD) including atherosclerosis is the leading cause of death worldwide. As CVDs and atherosclerosis develop, plaques begin to form in the blood vessels and become calcified. Calcification within the vasculature and atherosclerotic plaques have been correlated with rupture and consequently, acute myocardial infarction. However, current imaging methods to identify vascular calcification have limitations in determining plaque composition and structure. Nanoparticles can overcome these limitations due to their versatility and ability to incorporate a wide range of targeting and contrast agents. In this review, we summarize the current understanding of calcification in atherosclerosis, their role in instigating plaque instability, and clinical methodologies to detect and analyze vascular calcification. In addition, we highlight the potential of calcium-targeting ligands and nanoparticles to create novel calcium-detecting tools.

Lay Summary

Atherosclerosis is one of the major contributors of ischemic heart disease and stroke, which remain the world’s leading cause of death. Atherosclerosis is characterized by the chronic buildup of plaque and occlusion of the arteries. Over time, blood vessels become calcified, losing the elasticity and compliance that is critical to vascular health. Current diagnostic methods to detect calcification are limited to invasive imaging procedures with potentially fatal complications or methods with inadequate sensitivity in identifying plaque composition. Notably, recent work in calcium-detecting nanoparticles show promise as useful diagnostic tools for cardiovascular disease. In this review, we discuss the role of calcification in cardiovascular diseases, current imaging technologies for the detection of calcification, and the potential of nanoparticles as diagnostic and therapeutic agents.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    Leopold JA. Vascular calcification: mechanisms of vascular smooth muscle cell calcification. Trends Cardiovasc Med. 2015;25(4):267–74. https://doi.org/10.1016/j.tcm.2014.10.021.

    Google Scholar 

  2. 2.

    Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart disease and stroke statistics—2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67–e492. https://doi.org/10.1161/CIR.0000000000000558.

    Google Scholar 

  3. 3.

    Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part II. Circulation. 2003;108(15):1772–8. https://doi.org/10.1161/01.CIR.0000087481.55887.C9.

    Google Scholar 

  4. 4.

    Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J. 2013;34(10):719–28. https://doi.org/10.1093/eurheartj/ehs411.

    Google Scholar 

  5. 5.

    Libby P, Pasterkamp G. Requiem for the ‘vulnerable plaque’. Eur Heart J. 2015;36(43):2984–7. https://doi.org/10.1093/eurheartj/ehv349.

    Google Scholar 

  6. 6.

    Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364(3):226–35. https://doi.org/10.1056/NEJMoa1002358.

    Google Scholar 

  7. 7.

    Pasterkamp G, Schoneveld AH, van der Wal AC, Haudenschild CC, Clarijs RJ, Becker AE, et al. Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. J Am Coll Cardiol. 1998;32(3):655–62.

    Google Scholar 

  8. 8.

    Zhu D, Mackenzie NC, Farquharson C, Macrae VE. Mechanisms and clinical consequences of vascular calcification. Front Endocrinol (Lausanne). 2012;3:95. https://doi.org/10.3389/fendo.2012.00095.

    Google Scholar 

  9. 9.

    Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol. 2004;24(7):1161–70. https://doi.org/10.1161/01.ATV.0000133194.94939.42.

    Google Scholar 

  10. 10.

    Yu PJ, Skolnick A, Ferrari G, Heretis K, Mignatti P, Pintucci G, et al. Correlation between plasma osteopontin levels and aortic valve calcification: potential insights into the pathogenesis of aortic valve calcification and stenosis. J Thorac Cardiovasc Surg. 2009;138(1):196–9. https://doi.org/10.1016/j.jtcvs.2008.10.045.

    Google Scholar 

  11. 11.

    Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J, Fitzpatrick LA, et al. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol. 1998;31(1):126–33.

    Google Scholar 

  12. 12.

    Ehara S, Kobayashi Y, Yoshiyama M, Shimada K, Shimada Y, Fukuda D, et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation. 2004;110(22):3424–9. https://doi.org/10.1161/01.CIR.0000148131.41425.E9.

    Google Scholar 

  13. 13.

    Hoshino T, Chow LA, Hsu JJ, Perlowski AA, Abedin M, Tobis J, et al. Mechanical stress analysis of a rigid inclusion in distensible material: a model of atherosclerotic calcification and plaque vulnerability. Am J Physiol Heart Circ Physiol. 2009;297(2):H802–10. https://doi.org/10.1152/ajpheart.00318.2009.

    Google Scholar 

  14. 14.

    Lutgens E, van Suylen RJ, Faber BC, Gijbels MJ, Eurlings PM, Bijnens AP, et al. Atherosclerotic plaque rupture: local or systemic process? Arterioscler Thromb Vasc Biol. 2003;23(12):2123–30. https://doi.org/10.1161/01.ATV.0000097783.01596.E2.

    Google Scholar 

  15. 15.

    Sage AP, Tintut Y, Demer LL. Regulatory mechanisms in vascular calcification. Nat Rev Cardiol. 2010;7(9):528–36. https://doi.org/10.1038/nrcardio.2010.115.

    Google Scholar 

  16. 16.

    Mintz GS. Intravascular imaging of coronary calcification and its clinical implications. JACC Cardiovasc Imaging. 2015;8(4):461–71. https://doi.org/10.1016/j.jcmg.2015.02.003.

    Google Scholar 

  17. 17.

    Motro M, Shemesh J. Calcium channel blocker nifedipine slows down progression of coronary calcification in hypertensive patients compared with diuretics. Hypertension. 2001;37(6):1410–3.

    Google Scholar 

  18. 18.

    Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007;356(25):2591–602. https://doi.org/10.1056/NEJMoa071513.

    Google Scholar 

  19. 19.

    de Costa R Jr, Mintz GS, Carlier SG, Mehran R, Teirstein P, Sano K, et al. Nonrandomized comparison of coronary stenting under intravascular ultrasound guidance of direct stenting without predilation versus conventional predilation with a semi-compliant balloon versus predilation with a new scoring balloon. Am J Cardiol. 2007;100(5):812–7. https://doi.org/10.1016/j.amjcard.2007.03.100.

    Google Scholar 

  20. 20.

    Seo A, Fujii T, Inoue T, Onoda S, Koga A, Tanaka Y, et al. Initial and long-term outcomes of sirolimus-eluting stents for calcified lesions compared with bare-metal stents. Int Heart J. 2007;48(2):137–47.

    Google Scholar 

  21. 21.

    Khattab AA, Otto A, Hochadel M, Toelg R, Geist V, Richardt G. Drug-eluting stents versus bare metal stents following rotational atherectomy for heavily calcified coronary lesions: late angiographic and clinical follow-up results. J Interv Cardiol. 2007;20(2):100–6. https://doi.org/10.1111/j.1540-8183.2007.00243.x.

    Google Scholar 

  22. 22.

    Madhavan MV, Tarigopula M, Mintz GS, Maehara A, Stone GW, Genereux P. Coronary artery calcification: pathogenesis and prognostic implications. J Am Coll Cardiol. 2014;63(17):1703–14. https://doi.org/10.1016/j.jacc.2014.01.017.

    Google Scholar 

  23. 23.

    Biju V. Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. Chem Soc Rev. 2014;43(3):744–64. https://doi.org/10.1039/c3cs60273g.

    Google Scholar 

  24. 24.

    Sperling RA, Parak WJ. Surface modification, functionalization and bioconjugation of colloidal inorganic nanoparticles. Philos Trans A Math Phys Eng Sci. 2010;368(1915):1333–83. https://doi.org/10.1098/rsta.2009.0273.

    Google Scholar 

  25. 25.

    Chen J, Saeki F, Wiley BJ, Cang H, Cobb MJ, Li ZY, et al. Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents. Nano Lett. 2005;5(3):473–7. https://doi.org/10.1021/nl047950t.

    Google Scholar 

  26. 26.

    Bogart LK, Pourroy G, Murphy CJ, Puntes V, Pellegrino T, Rosenblum D, et al. Nanoparticles for imaging, sensing, and therapeutic intervention. ACS Nano. 2014;8(4):3107–22. https://doi.org/10.1021/nn500962q.

    Google Scholar 

  27. 27.

    Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33(9):941–51. https://doi.org/10.1038/nbt.3330.

    Google Scholar 

  28. 28.

    Sharma G, She ZG, Valenta DT, Stallcup WB, Smith JW. Targeting of macrophage foam cells in atherosclerotic plaque using oligonucleotide-functionalized nanoparticles. Nano Life. 2010;1(3–4):207–14. https://doi.org/10.1142/S1793984410000183.

    Google Scholar 

  29. 29.

    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(6):462–75. https://doi.org/10.1093/eurheartj/ehs366.

    Google Scholar 

  30. 30.

    Sanchez-Gaytan BL, Fay F, Lobatto ME, Tang J, Ouimet M, Kim Y, et al. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages. Bioconjug Chem. 2015;26(3):443–51. https://doi.org/10.1021/bc500517k.

    Google Scholar 

  31. 31.

    Niu M, Naguib YW, Aldayel AM, Shi YC, Hursting SD, Hersh MA, et al. Biodistribution and in vivo activities of tumor-associated macrophage-targeting nanoparticles incorporated with doxorubicin. Mol Pharm. 2014;11(12):4425–36. https://doi.org/10.1021/mp500565q.

    Google Scholar 

  32. 32.

    Yoo SP, Pineda F, Barrett JC, Poon C, Tirrell M, Chung EJ. Gadolinium-functionalized peptide amphiphile micelles for multimodal imaging of atherosclerotic lesions. ACS Omega. 2016;1(5):996–1003. https://doi.org/10.1021/acsomega.6b00210.

    Google Scholar 

  33. 33.

    Anselmo AC, Modery-Pawlowski CL, Menegatti S, Kumar S, Vogus DR, Tian LL, et al. Platelet-like nanoparticles: mimicking shape, flexibility, and surface biology of platelets to target vascular injuries. ACS Nano. 2014;8(11):11243–53. https://doi.org/10.1021/nn503732m.

    Google Scholar 

  34. 34.

    Charoenphol P, Huang RB, Eniola-Adefeso O. Potential role of size and hemodynamics in the efficacy of vascular-targeted spherical drug carriers. Biomaterials. 2010;31(6):1392–402. https://doi.org/10.1016/j.biomaterials.2009.11.007.

    Google Scholar 

  35. 35.

    Dahlman JE, Barnes C, Khan O, Thiriot A, Jhunjunwala S, Shaw TE, et al. In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight. Nat Nanotechnol. 2014;9(8):648–55. https://doi.org/10.1038/nnano.2014.84.

    Google Scholar 

  36. 36.

    Tsourkas A, Shinde-Patil VR, Kelly KA, Patel P, Wolley A, Allport JR, et al. In vivo imaging of activated endothelium using an anti-VCAM-1 magnetooptical probe. Bioconjug Chem. 2005;16(3):576–81. https://doi.org/10.1021/bc050002e.

    Google Scholar 

  37. 37.

    Bruckman MA, Jiang K, Simpson EJ, Randolph LN, Luyt LG, Yu X, et al. Dual-modal magnetic resonance and fluorescence imaging of atherosclerotic plaques in vivo using VCAM-1 targeted tobacco mosaic virus. Nano Lett. 2014;14(3):1551–8. https://doi.org/10.1021/nl404816m.

    Google Scholar 

  38. 38.

    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(3):379–87. https://doi.org/10.1161/CIRCULATIONAHA.107.741181.

    Google Scholar 

  39. 39.

    Chung EJ, Tirrell M. Recent advances in targeted, self-assembling nanoparticles to address vascular damage due to atherosclerosis. Adv Healthc Mater. 2015;4(16):2408–22. https://doi.org/10.1002/adhm.201500126.

    Google Scholar 

  40. 40.

    Khodabandehlou K, Masehi-Lano JJ, Poon C, Wang J, Chung EJ. Targeting cell adhesion molecules with nanoparticles using in vivo and flow-based in vitro models of atherosclerosis. Exp Biol Med (Maywood). 2017;242(8):799–812. https://doi.org/10.1177/1535370217693116.

    Google Scholar 

  41. 41.

    Kumar S, Kim CW, Simmons RD, Jo H. Role of flow-sensitive microRNAs in endothelial dysfunction and atherosclerosis: mechanosensitive athero-miRs. Arterioscler Thromb Vasc Biol. 2014;34(10):2206–16. https://doi.org/10.1161/ATVBAHA.114.303425.

    Google Scholar 

  42. 42.

    Tsigkas N, Kidambi S, Tawakol A, Chatzizisis YS. Drug-loaded particles: “Trojan horses” in the therapy of atherosclerosis. Atherosclerosis. 2016;251:528–30. https://doi.org/10.1016/j.atherosclerosis.2016.06.050.

    Google Scholar 

  43. 43.

    Ross RD, Roeder RK. Binding affinity of surface functionalized gold nanoparticles to hydroxyapatite. J Biomed Mater Res A. 2011;99(1):58–66. https://doi.org/10.1002/jbm.a.33165.

    Google Scholar 

  44. 44.

    de Miguel L, Popa I, Noiray M, Caudron E, Arpinati L, Desmaele D, et al. Osteotropic polypeptide nanoparticles with dual hydroxyapatite binding properties and controlled cisplatin delivery. Pharm Res. 2015;32(5):1794–803. https://doi.org/10.1007/s11095-014-1576-z.

    Google Scholar 

  45. 45.

    Lee JS, Tung CH. Osteocalcin biomimic recognizes bone hydroxyapatite. Chembiochem. 2011;12(11):1669–73. https://doi.org/10.1002/cbic.201100162.

    Google Scholar 

  46. 46.

    Gilbert M, Shaw WJ, Long JR, Nelson K, Drobny GP, Giachelli CM, et al. Chimeric peptides of statherin and osteopontin that bind hydroxyapatite and mediate cell adhesion. J Biol Chem. 2000;275(21):16213–8. https://doi.org/10.1074/jbc.M001773200.

    Google Scholar 

  47. 47.

    Fujisawa R, Kuboki Y. Preferential adsorption of dentin and bone acidic proteins on the (100) face of hydroxyapatite crystals. Biochim Biophys Acta. 1991;1075(1):56–60.

    Google Scholar 

  48. 48.

    Fujisawa R, Wada Y, Nodasaka Y, Kuboki Y. Acidic amino acid-rich sequences as binding sites of osteonectin to hydroxyapatite crystals. Biochim Biophys Acta. 1996;1292(1):53–60.

    Google Scholar 

  49. 49.

    Johnsson M, Levine MJ, Nancollas GH. Hydroxyapatite binding domains in salivary proteins. Crit Rev Oral Biol Med. 1993;4(3–4):371–8.

    Google Scholar 

  50. 50.

    Boskey AL. Osteopontin and related phosphorylated sialoproteins: effects on mineralization. Ann N Y Acad Sci. 1995;760:249–56.

    Google Scholar 

  51. 51.

    Chen NX, O'Neill KD, Chen X, Moe SM. Annexin-mediated matrix vesicle calcification in vascular smooth muscle cells. J Bone Miner Res. 2008;23(11):1798–805. https://doi.org/10.1359/jbmr.080604.

    Google Scholar 

  52. 52.

    Demer LL, Watson KE, Bostrom K. Mechanism of calcification in atherosclerosis. Trends Cardiovasc Med. 1994;4(1):45–9. https://doi.org/10.1016/1050-1738(94)90025-6.

    Google Scholar 

  53. 53.

    Hsu JJ, Lim J, Tintut Y, Demer LL. Cell-matrix mechanics and pattern formation in inflammatory cardiovascular calcification. Heart. 2016;102(21):1710–5. https://doi.org/10.1136/heartjnl-2016-309667.

    Google Scholar 

  54. 54.

    Kapustin AN, Davies JD, Reynolds JL, McNair R, Jones GT, Sidibe A, et al. Calcium regulates key components of vascular smooth muscle cell-derived matrix vesicles to enhance mineralization. Circ Res. 2011;109(1):e1–12. https://doi.org/10.1161/CIRCRESAHA.110.238808.

    Google Scholar 

  55. 55.

    Bostrom KI, Rajamannan NM, Towler DA. The regulation of valvular and vascular sclerosis by osteogenic morphogens. Circ Res. 2011;109(5):564–77. https://doi.org/10.1161/CIRCRESAHA.110.234278.

    Google Scholar 

  56. 56.

    Hunt JL, Fairman R, Mitchell ME, Carpenter JP, Golden M, Khalapyan T, et al. Bone formation in carotid plaques: a clinicopathological study. Stroke. 2002;33(5):1214–9.

    Google Scholar 

  57. 57.

    Schlieper G, Schurgers L, Brandenburg V, Reutelingsperger C, Floege J. Vascular calcification in chronic kidney disease: an update. Nephrol Dial Transplant. 2016;31(1):31–9. https://doi.org/10.1093/ndt/gfv111.

    Google Scholar 

  58. 58.

    Al-Aly Z, Shao JS, Lai CF, Huang E, Cai J, Behrmann A, et al. Aortic Msx2-Wnt calcification cascade is regulated by TNF-alpha-dependent signals in diabetic Ldlr−/− mice. Arterioscler Thromb Vasc Biol. 2007;27(12):2589–96. https://doi.org/10.1161/ATVBAHA.107.153668.

    Google Scholar 

  59. 59.

    Yang X, Meng X, Su X, Mauchley DC, Ao L, Cleveland JC Jr, et al. Bone morphogenic protein 2 induces Runx2 and osteopontin expression in human aortic valve interstitial cells: role of Smad1 and extracellular signal-regulated kinase 1/2. J Thorac Cardiovasc Surg. 2009;138(4):1008–15. https://doi.org/10.1016/j.jtcvs.2009.06.024.

    Google Scholar 

  60. 60.

    Choi ST, Kim JH, Kang EJ, Lee SW, Park MC, Park YB, et al. Osteopontin might be involved in bone remodelling rather than in inflammation in ankylosing spondylitis. Rheumatology (Oxford). 2008;47(12):1775–9. https://doi.org/10.1093/rheumatology/ken385.

    Google Scholar 

  61. 61.

    Lomashvili KA, Wang X, Wallin R, O'Neill WC. Matrix Gla protein metabolism in vascular smooth muscle and role in uremic vascular calcification. J Biol Chem. 2011;286(33):28715–22. https://doi.org/10.1074/jbc.M111.251462.

    Google Scholar 

  62. 62.

    Speer MY, Yang HY, Brabb T, Leaf E, Look A, Lin WL, et al. Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circ Res. 2009;104(6):733–41. https://doi.org/10.1161/CIRCRESAHA.108.183053.

    Google Scholar 

  63. 63.

    Hutcheson JD, Goettsch C, Bertazzo S, Maldonado N, Ruiz JL, Goh W, et al. Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques. Nat Mater. 2016;15(3):335–43. https://doi.org/10.1038/nmat4519.

    Google Scholar 

  64. 64.

    Demer LL, Tintut Y. Inflammatory, metabolic, and genetic mechanisms of vascular calcification. Arterioscler Thromb Vasc Biol. 2014;34(4):715–23. https://doi.org/10.1161/ATVBAHA.113.302070.

    Google Scholar 

  65. 65.

    Genge BR, Wu LNY, Wuthier RE. Differential fractionation of matrix vesicle proteins—further characterization of the acidic phospholipid-dependent Ca2+-binding proteins. J Biol Chem. 1990;265(8):4703–10.

    Google Scholar 

  66. 66.

    Kapustin AN, Shanahan CM. Calcium regulation of vascular smooth muscle cell-derived matrix vesicles. Trends Cardiovas Med. 2012;22(5):133–7. https://doi.org/10.1016/j.tcm.2012.07.009.

    Google Scholar 

  67. 67.

    Krohn JB, Hutcheson JD, Martinez-Martinez E, Aikawa E. Extracellular vesicles in cardiovascular calcification: expanding current paradigms. J Physiol. 2016;594(11):2895–903. https://doi.org/10.1113/JP271338.

    Google Scholar 

  68. 68.

    Persy V, D'Haese P. Vascular calcification and bone disease: the calcification paradox. Trends Mol Med. 2009;15(9):405–16. https://doi.org/10.1016/j.molmed.2009.07.001.

    Google Scholar 

  69. 69.

    Patrick F, Ross JC, Alvarez JI, Sander D, Butler WT, Farach-Carson MC, et al. Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integration potentiate bone resorption. J Biol Chem. 1993;268:9901–7.

    Google Scholar 

  70. 70.

    Guiqian Chen CD, Li Y-P. TGF-beta and BMP signaling in osteoblastt differentiation and bone formation. Int J Biol Sci. 2012;8(2):272–88.

    Google Scholar 

  71. 71.

    Hutcheson JD, Maldonado N, Aikawa E. Small entities with large impact: microcalcifications and atherosclerotic plaque vulnerability. Curr Opin Lipidol. 2014;25(5):327–32. https://doi.org/10.1097/MOL.0000000000000105.

    Google Scholar 

  72. 72.

    Richardson PD, Davies MJ, Born GV. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet. 1989;2(8669):941–4.

    Google Scholar 

  73. 73.

    Calvert PA, Liew TV, Gorenne I, Clarke M, Costopoulos C, Obaid DR, et al. Leukocyte telomere length is associated with high-risk plaques on virtual histology intravascular ultrasound and increased proinflammatory activity. Arterioscler Thromb Vasc Biol. 2011;31(9):2157–64. https://doi.org/10.1161/ATVBAHA.111.229237.

    Google Scholar 

  74. 74.

    Kelly-Arnold A, Maldonado N, Laudier D, Aikawa E, Cardoso L, Weinbaum S. Revised microcalcification hypothesis for fibrous cap rupture in human coronary arteries. Proc Natl Acad Sci U S A. 2013;110(26):10741–6. https://doi.org/10.1073/pnas.1308814110.

    Google Scholar 

  75. 75.

    Maldonado N, Kelly-Arnold A, Vengrenyuk Y, Laudier D, Fallon JT, Virmani R, et al. A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture. Am J Physiol Heart Circ Physiol. 2012;303(5):H619–28. https://doi.org/10.1152/ajpheart.00036.2012.

    Google Scholar 

  76. 76.

    Demer LL, Tintut Y, Nguyen KL, Hsiai T, Lee JT. Rigor and reproducibility in analysis of vascular calcification. Circ Res. 2017;120(8):1240–2. https://doi.org/10.1161/CIRCRESAHA.116.310326.

    Google Scholar 

  77. 77.

    Bittencourt MS, Cerci RJ. Statin effects on atherosclerotic plaques: regression or healing? BMC Med. 2015;13:260. https://doi.org/10.1186/s12916-015-0499-9.

    Google Scholar 

  78. 78.

    Imoto K, Hiro T, Fujii T, Murashige A, Fukumoto Y, Hashimoto G, et al. Longitudinal structural determinants of atherosclerotic plaque vulnerability: a computational analysis of stress distribution using vessel models and three-dimensional intravascular ultrasound imaging. J Am Coll Cardiol. 2005;46(8):1507–15. https://doi.org/10.1016/j.jacc.2005.06.069.

    Google Scholar 

  79. 79.

    Messika-Zeitoun D, Aubry MC, Detaint D, Bielak LF, Peyser PA, Sheedy PF, et al. Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography. Circulation. 2004;110(3):356–62. https://doi.org/10.1161/01.CIR.0000135469.82545.D0.

    Google Scholar 

  80. 80.

    Hecht HS, Budoff MJ, Berman DS, Ehrlich J, Rumberger JA. Coronary artery calcium scanning: clinical paradigms for cardiac risk assessment and treatment. Am Heart J. 2006;151(6):1139–46. https://doi.org/10.1016/j.ahj.2005.07.018.

    Google Scholar 

  81. 81.

    Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010;56(25):e50–103. https://doi.org/10.1016/j.jacc.2010.09.001.

    Google Scholar 

  82. 82.

    Rumberger JA, Kaufman L. A rosetta stone for coronary calcium risk stratification: agatston, volume, and mass scores in 11,490 individuals. AJR Am J Roentgenol. 2003;181(3):743–8. https://doi.org/10.2214/ajr.181.3.1810743.

    Google Scholar 

  83. 83.

    Callister TQ, Cooil B, Raya SP, Lippolis NJ, Russo DJ, Raggi P. Coronary artery disease: improved reproducibility of calcium scoring with an electron-beam CT volumetric method. Radiology. 1998;208(3):807–14. https://doi.org/10.1148/radiology.208.3.9722864.

    Google Scholar 

  84. 84.

    Sanz J, Fayad ZA. Imaging of atherosclerotic cardiovascular disease. Nature. 2008;451(7181):953–7. https://doi.org/10.1038/nature06803.

    Google Scholar 

  85. 85.

    Saam T, Ferguson MS, Yarnykh VL, Takaya N, Xu D, Polissar NL, et al. Quantitative evaluation of carotid plaque composition by in vivo MRI. Arterioscler Thromb Vasc Biol. 2005;25(1):234–9. https://doi.org/10.1161/01.ATV.0000149867.61851.31.

    Google Scholar 

  86. 86.

    Kramer CM, Anderson JD. MRI of atherosclerosis: diagnosis and monitoring therapy. Expert Rev Cardiovasc Ther. 2007;5(1):69–80. https://doi.org/10.1586/14779072.5.1.69.

    Google Scholar 

  87. 87.

    Friedrich GJ, Moes NY, Muhlberger VA, Gabl C, Mikuz G, Hausmann D, et al. Detection of intralesional calcium by intracoronary ultrasound depends on the histologic pattern. Am Heart J. 1994;128(3):435–41.

    Google Scholar 

  88. 88.

    Johnson RC, Leopold JA, Loscalzo J. Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res. 2006;99(10):1044–59. https://doi.org/10.1161/01.RES.0000249379.55535.21.

    Google Scholar 

  89. 89.

    Prati F, Regar E, Mintz GS, Arbustini E, Di Mario C, Jang IK, et al. Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur Heart J. 2010;31(4):401–15. https://doi.org/10.1093/eurheartj/ehp433.

    Google Scholar 

  90. 90.

    Yabushita H, Bouma BE, Houser SL, Aretz HT, Jang IK, Schlendorf KH, et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation. 2002;106(13):1640–5.

    Google Scholar 

  91. 91.

    Jang IK, Bouma BE, Kang DH, Park SJ, Park SW, Seung KB, et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J Am Coll Cardiol. 2002;39(4):604–9.

    Google Scholar 

  92. 92.

    Orbay H, Hong H, Zhang Y, Cai W. Positron emission tomography imaging of atherosclerosis. Theranostics. 2013;3(11):894–902. https://doi.org/10.7150/thno.5506.

    Google Scholar 

  93. 93.

    Derlin T, Richter U, Bannas P, Begemann P, Buchert R, Mester J, et al. Feasibility of 18F-sodium fluoride PET/CT for imaging of atherosclerotic plaque. J Nucl Med. 2010;51(6):862–5. https://doi.org/10.2967/jnumed.110.076471.

    Google Scholar 

  94. 94.

    Dweck MR, Jones C, Joshi NV, Fletcher AM, Richardson H, White A, et al. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation. 2012;125(1):76–86. https://doi.org/10.1161/CIRCULATIONAHA.111.051052.

    Google Scholar 

  95. 95.

    Beheshti M, Saboury B, Mehta NN, Torigian DA, Werner T, Mohler E, et al. Detection and global quantification of cardiovascular molecular calcification by fluoro18-fluoride positron emission tomography/computed tomography—a novel concept. Hell J Nucl Med. 2011;14(2):114–20.

    Google Scholar 

  96. 96.

    Allen S, Liu YG, Scott E. Engineering nanomaterials to address cell-mediated inflammation in atherosclerosis. Regen Eng Transl Med. 2016;2(1):37–50. https://doi.org/10.1007/s40883-016-0012-9.

    Google Scholar 

  97. 97.

    Christopher AF, Kaur RP, Kaur G, Kaur A, Gupta V, Bansal P. MicroRNA therapeutics: discovering novel targets and developing specific therapy. Perspect Clin Res. 2016;7(2):68–74. https://doi.org/10.4103/2229-3485.179431.

    Google Scholar 

  98. 98.

    Kheirolomoom A, Kim CW, Seo JW, Kumar S, Son DJ, Gagnon MK, et al. Multifunctional nanoparticles facilitate molecular targeting and miRNA delivery to inhibit atherosclerosis in ApoE(−/−) mice. ACS Nano. 2015;9(9):8885–97. https://doi.org/10.1021/acsnano.5b02611.

    Google Scholar 

  99. 99.

    Lee JS, Morrisett JD, Tung CH. Detection of hydroxyapatite in calcified cardiovascular tissues. Atherosclerosis. 2012;224(2):340–7. https://doi.org/10.1016/j.atherosclerosis.2012.07.023.

    Google Scholar 

  100. 100.

    Schulz RB, Semmler W. Fundamentals of optical imaging. Handb Exp Pharmacol. 2008;185 Pt 1:3–22. https://doi.org/10.1007/978-3-540-72718-7_1.

    Google Scholar 

  101. 101.

    Aikawa E, Nahrendorf M, Sosnovik D, Lok VM, Jaffer FA, Aikawa M, et al. Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation. 2007;115(3):377–86. https://doi.org/10.1161/CIRCULATIONAHA.106.654913.

    Google Scholar 

  102. 102.

    Pellicoab J, AVL-V M, Benitoa JM, García-Segurab V, Fusterc J, Ruiz-Cabelloab, et al. Microwave-driven synthesis of bisphosphonate nanoparticles allows in vivo visualisation of atherosclerotic plaque. RSC Adv. 2014;5:1661–5. https://doi.org/10.1039/C4RA13824D.

    Google Scholar 

  103. 103.

    Ho AM, Johnson MD, Kingsley DM. Role of the mouse ank gene in control of tissue calcification and arthritis. Science. 2000;289(5477):265–70.

    Google Scholar 

  104. 104.

    Lei Y, Nosoudi N, Vyavahare N. Targeted chelation therapy with EDTA-loaded albumin nanoparticles regresses arterial calcification without causing systemic side effects. J Control Release. 2014;196:79–86. https://doi.org/10.1016/j.jconrel.2014.09.029.

    Google Scholar 

  105. 105.

    Li N, Song J, Zhu G, Shi X, Wang Y. Alendronate conjugated nanoparticles for calcification targeting. Colloids Surf B Biointerfaces. 2016;142:344–50. https://doi.org/10.1016/j.colsurfb.2016.03.015.

    Google Scholar 

  106. 106.

    Choi SW, Kim JH. Design of surface-modified poly(D,L-lactide-co-glycolide) nanoparticles for targeted drug delivery to bone. J Control Release. 2007;122(1):24–30. https://doi.org/10.1016/j.jconrel.2007.06.003.

    Google Scholar 

  107. 107.

    Thamake SI, Raut SL, Gryczynski Z, Ranjan AP, Vishwanatha JK. Alendronate coated poly-lactic-co-glycolic acid (PLGA) nanoparticles for active targeting of metastatic breast cancer. Biomaterials. 2012;33(29):7164–73. https://doi.org/10.1016/j.biomaterials.2012.06.026.

    Google Scholar 

  108. 108.

    Swami A, Reagan MR, Basto P, Mishima Y, Kamaly N, Glavey S, et al. Engineered nanomedicine for myeloma and bone microenvironment targeting. Proc Natl Acad Sci U S A. 2014;111(28):10287–92. https://doi.org/10.1073/pnas.1401337111.

    Google Scholar 

  109. 109.

    Hengst V, Oussoren C, Kissel T, Storm G. Bone targeting potential of bisphosphonate-targeted liposomes. Preparation, characterization and hydroxyapatite binding in vitro. Int J Pharm. 2007;331(2):224–7. https://doi.org/10.1016/j.ijpharm.2006.11.024.

    Google Scholar 

  110. 110.

    Sanchez F, Zhang L. Molecular dynamics modeling of the interface between surface functionalized graphitic structures and calcium-silicate-hydrate: interaction energies, structure, and dynamics. J Colloid Interface Sci. 2008;323(2):349–58. https://doi.org/10.1016/j.jcis.2008.04.023.

    Google Scholar 

  111. 111.

    Murphy MB, Hartgerink JD, Goepferich A, Mikos AG. Synthesis and in vitro hydroxyapatite binding of peptides conjugated to calcium-binding moieties. Biomacromolecules. 2007;8(7):2237–43. https://doi.org/10.1021/bm070121s.

    Google Scholar 

  112. 112.

    Torchilin VP. Multifunctional nanocarriers. Adv Drug Deliv Rev. 2006;58(14):1532–55. https://doi.org/10.1016/j.addr.2006.09.009.

    Google Scholar 

  113. 113.

    Mao J, Shi X, Wu YB, Gong SQ. Identification of specific hydroxyapatite {001} binding heptapeptide by phage display and its nucleation effect. Materials (Basel) 2016;9(8). https://doi.org/10.3390/ma9080700.

  114. 114.

    Roy MD, Amis EJ, Becker ML. Identification of a highly specific hydroxyapatite-binding peptide using phage display. Adv Mater. 2008;20(10):1830–6.

    Google Scholar 

  115. 115.

    Weiger MC, Park JJ, Roy MD, Stafford CM, Karim A, Becker ML. Quantification of the binding affinity of a specific hydroxyapatite binding peptide. Biomaterials. 2010;31(11):2955–63. https://doi.org/10.1016/j.biomaterials.2010.01.012.

    Google Scholar 

  116. 116.

    Hauschka PV, Carr SA. Calcium-dependent alpha-helical structure in osteocalcin. Biochemistry. 1982;21(10):2538–47.

    Google Scholar 

  117. 117.

    Meisel CL, Bainbridge P, Mitsouras D, Wong JY. Targeted nanoparticle binding to hydroxyapatite in a high serum environment for early detection of heart disease. ACS Appl Nano Mater. 2018;1:4927–39. https://doi.org/10.1021/acsanm.8b01099.

    Google Scholar 

  118. 118.

    Bain JL, Culpepper BK, Reddy MS, Bellis SL. Comparing variable-length polyglutamate domains to anchor an osteoinductive collagen-mimetic peptide to diverse bone grafting materials. Int J Oral Maxillofac Implants. 2014;29(6):1437–45. https://doi.org/10.11607/jomi.3759.

    Google Scholar 

  119. 119.

    Bain JL, Bonvallet PP, Abou-Arraj RV, Schupbach P, Reddy MS, Bellis SL. Enhancement of the regenerative potential of anorganic bovine bone graft utilizing a polyglutamate-modified BMP2 peptide with improved binding to calcium-containing materials. Tissue Eng A. 2015;21(17–18):2426–36. https://doi.org/10.1089/ten.TEA.2015.0160.

    Google Scholar 

  120. 120.

    Culpepper BK, Bonvallet PP, Reddy MS, Ponnazhagan S, Bellis SL. Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone. Biomaterials. 2013;34(5):1506–13. https://doi.org/10.1016/j.biomaterials.2012.10.046.

    Google Scholar 

Download references

Funding

The authors would like to acknowledge the financial support from the Women in Science and Engineering Program at University of Southern California (USC) for undergraduate research awarded to SC and Gabilan Assistant Professorship awarded to EJC. In addition, we acknowledge the financial support from the L. K. Whittier Foundation and the National Heart, Lung, and Blood Institute (NHLBI), R00HL124279, awarded to EJC.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Eun Ji Chung.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chin, D.D., Chowdhuri, S. & Chung, E.J. Calcium-Binding Nanoparticles for Vascular Disease. Regen. Eng. Transl. Med. 5, 74–85 (2019). https://doi.org/10.1007/s40883-018-0083-x

Download citation

Keywords

  • Nanoparticle
  • Cardiovascular disease
  • Vascular calcification
  • Imaging
  • Drug delivery
  • Peptides