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Personalised deposition maps for micro- and nanoparticles targeting an atherosclerotic plaque: attributions to the receptor-mediated adsorption on the inflamed endothelial cells

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Abstract

Endothelial inflammation as a prominent precursor to atherosclerosis elicits a distinct pathological surface expression of particular vascular proteins. To exhibit a site-specific behaviour, micro- and nanoparticles, as carriers of therapeutics or imaging agents, can distinguish and use these proteins as targeted docking sites. Here, a computational patient-specific model capturing the exclusive luminal qualities has been developed to study the transport and adsorption of particles decorated with proper antibodies over an atherosclerotic plaque located in the LAD artery of the patient. Particles, in nano- and micron sizes, have been decorated with Sialyl Lewisx (sLex), P-selectin aptamer (PSA), and ICAM-1 antibody (abICAM) to target the three of the most well-known endothelial adhesion proteins that display pathological expressions on the plaque surface, namely E-selectin, ICAM-1, and P-selectin. We learned that in the receptor-mediated adhesive dynamics in pathological contexts, parameters such as specific diffusivity of ligand–receptor pairs and the affinity constant play crucial roles in the final amount and homogeneity of surface density of adsorbed particles (SDA). In spite of ascending nature of SDAs with the increase in particle size, our model specified that the alteration in results due to increase in particle diameter can be insignificant depending upon the special parameters associated with the type of ligand–receptor bonds. Also, the combination of 95.1% sLex and 4.9% PSA ligands for dual-targeting 800-nm particles was introduced as the optimal decorating arrangement for which the surface of plaque experiences a significant SDA along with a homogeneously improved deposition pattern. Finally, the key results of this work were compared with the results of similar experiments in a pulsatile flow chamber and a relevant in vivo test.

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References

  • Amr A, Kayvanpour E, Sedaghat-Hamedani F, Passerini T, Mihalef V, Lai A, Neumann D, Georgescu B, Buss S, Mereles D, Zitron E, Posch AE, Wurstle M, Mansi T, Katus HA, Meder B (2016) Personalized computer simulation of diastolic function in heart failure. Genomics Proteomics Bioinf 14(4):244–252

    Article  Google Scholar 

  • Anderson DG (1965) Iterative procedures for nonlinear integral equations. J ACM 12(4):547–560

    Article  MathSciNet  MATH  Google Scholar 

  • Ascher UM, Petzold LR (1988) Computer methods for ordinary differential equations and differential-algebraic equations. SIAM, Philadelphia

    MATH  Google Scholar 

  • Bell GI (1978) Models for the specific adhesion of cells to cells. Science 200(4342):618–627

    Article  Google Scholar 

  • Bell GI, Dembo M, Bongrand P (1984) Cell adhesion. Competition between nonspecific repulsion and specific bonding. Biophys J 45(6):1051–1064

    Article  Google Scholar 

  • Caballero AD, Laín S (2014) Numerical simulation of non-Newtonian blood flow dynamics in human thoracic aorta. Comput Methods Biomech Biomed Eng 18(11):1200–1216

    Article  Google Scholar 

  • Caputo KE, Lee D, King MR, Hammer DA (2007) Adhesive dynamics simulations of the shear threshold effect for leukocytes. Biophys J 92(3):787–797

    Article  Google Scholar 

  • Chang K-C, Hammer DA (2000) Adhesive dynamics simulations of Sialyl-Lewisx/E-selectin-mediated rolling in a cell-free system. Biophys J 79(4):1891–1902

    Article  Google Scholar 

  • Charoenphol P, Huang RB, Eniola-Adefeso O (2010) Potential role of size and hemodynamics in the efficacy of vascular-targeted spherical drug carriers. Biomaterials 31(6):1392–1402

    Article  Google Scholar 

  • Charoenphol P, Mocherla S, Bouis D, Namdee K, Pinsky DJ, Eniola-Adefeso O (2011) Targeting therapeutics to the vascular wall in atherosclerosis–carrier size matters. Atherosclerosis 217(2):364–370

    Article  Google Scholar 

  • Chen X, Wong R, Khalidov I, Wang AY, Leelawattanachai J, Wang Y, Jin MM (2011) Inflamed leukocyte-mimetic nanoparticles for molecular imaging of inflammation. Biomaterials 32(30):7651–7661

    Article  Google Scholar 

  • Curtiss CF, Hirschfelder JO (1952) Integration of Stiff Equations. Proc Natl Acad Sci USA 38(3):235–243

    Article  MathSciNet  MATH  Google Scholar 

  • Debakey ME, Lawrie GM, Glaeser DH (1985) Patterns of atherosclerosis and their surgical significance. Ann Surg 201(2):115–131

    Article  Google Scholar 

  • Decuzzi P, Ferrari M (2006) The adhesive strength of non-spherical particles mediated by specific interactions. Biomaterials 27(30):5307–5314

    Article  Google Scholar 

  • Decuzzi P, Pasqualini R, Arap W, Ferrari M (2009) Intravascular delivery of particulate systems: does geometry really matter? Pharm Res 26(1):235–243

    Article  Google Scholar 

  • Eniola AO, Willcox PJ, Hammer DA (2003) Interplay between rolling and firm adhesion elucidated with a cell-free system engineered with two distinct receptor-ligand pairs. Biophys J 85(4):2720–2731

    Article  Google Scholar 

  • Evans WE, McLeod HL (2003) Pharmacogenomics–drug disposition, drug targets, and side effects. N Engl J Med 348(6):538–549

    Article  Google Scholar 

  • Forouzandehmehr M, Shamloo A (2017) Margination and adhesion of micro- and nanoparticles in the coronary circulation: a step towards optimised drug carrier design. Biomech Model Mechanobiol 17(1):205–221

    Article  Google Scholar 

  • Ghosh S, Matsuoka Y, Asai Y, Hsin KY, Kitano H (2011) Software for systems biology: from tools to integrated platforms. Nat Rev Genet 12(12):821–832

    Article  Google Scholar 

  • Goldman AJ, Cox RG, Brenner H (1967) Slow viscous motion of a sphere parallel to a plane wall—II Couette flow. Chem Eng Sci 22(4):653–660

    Article  Google Scholar 

  • Goubergrits L, Wellnhofer E, Kertzscher U (2008) Choice and impact of a non-Newtonian blood model for wall shear stress profiling of coronary arteries. Springer, Berlin, pp 111–114

    Google Scholar 

  • Gradus-Pizlo I, Bigelow B, Mahomed Y, Sawada SG, Rieger K, Feigenbaum H (2003) Left anterior descending coronary artery wall thickness measured by high-frequency transthoracic and epicardial echocardiography includes adventitia. Am J Cardiol 91(1):27–32

    Article  Google Scholar 

  • Greineder CF, Howard MD, Carnemolla R, Cines DB, Muzykantov VR (2013) Advanced drug delivery systems for antithrombotic agents. Blood 122(9):1565–1575

    Article  Google Scholar 

  • Hammer DA, Apte SM (1992) Simulation of cell rolling and adhesion on surfaces in shear flow: general results and analysis of selectin-mediated neutrophil adhesion. Biophys J 63(1):35–57

    Article  Google Scholar 

  • Hossain SS, Hossainy SFA, Bazilevs Y, Calo VM, Hughes TJR (2011) Mathematical modeling of coupled drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls. Comput Mech 49(2):213–242

    Article  MathSciNet  MATH  Google Scholar 

  • Hossain SS, Zhang Y, Liang X, Hussain F, Ferrari M, Hughes TJ, Decuzzi P (2013) In silico vascular modeling for personalized nanoparticle delivery. Nanomedicine 8(3):343–357

    Article  Google Scholar 

  • Hossain SS, Hughes TJ, Decuzzi P (2014) Vascular deposition patterns for nanoparticles in an inflamed patient-specific arterial tree. Biomech Model Mechanobiol 13(3):585–597

    Article  Google Scholar 

  • Hossain SS, Zhang Y, Fu X, Brunner G, Singh J, Hughes TJ, Shah D, Decuzzi P (2015) Magnetic resonance imaging-based computational modelling of blood flow and nanomedicine deposition in patients with peripheral arterial disease. J R Soc Interface 12(106):20150001

    Article  Google Scholar 

  • Itu LM, Sharma P, Suciu C (2017) Patient-specific hemodynamic computations: application to personalized diagnosis of cardiovascular pathologies. Springer, Cham

    Book  Google Scholar 

  • Jin K, Luo Z, Zhang B, Pang Z (2018) Biomimetic nanoparticles for inflammation targeting. Acta Pharm Sin B 8(1):23–33

    Article  Google Scholar 

  • Johnston BM, Johnston PR, Corney S, Kilpatrick D (2004) Non-Newtonian blood flow in human right coronary arteries: steady state simulations. J Biomech 37(5):709–720

    Article  Google Scholar 

  • Karimi A, Navidbakhsh M, Faghihi S, Shojaei A, Hassani K (2013) A finite element investigation on plaque vulnerability in realistic healthy and atherosclerotic human coronary arteries. Proc Inst Mech Eng H 227(2):148–161

    Article  Google Scholar 

  • Karimi A, Navidbakhsh M, Shojaei A, Hassani K, Faghihi S (2014) Study of plaque vulnerability in coronary artery using Mooney–Rivlin model: a combination of finite element and experimental method, biomedical engineering: applications. Basis Commun 26(01):1450013

    Article  Google Scholar 

  • Kaufmann BA, Sanders JM, Davis C, Xie A, Aldred P, Sarembock IJ, Lindner JR (2007) Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1. Circulation 116(3):276–284

    Article  Google Scholar 

  • Kayvanpour E, Mansi T, Sedaghat-Hamedani F, Amr A, Neumann D, Georgescu B, Seegerer P, Kamen A, Haas J, Frese KS, Irawati M, Wirsz E, King V, Buss S, Mereles D, Zitron E, Keller A, Katus HA, Comaniciu D, Meder B (2015) Towards personalized cardiology: multi-scale modeling of the failing heart. PLoS ONE 10(7):e0134869

    Article  Google Scholar 

  • Kent DM, Hayward RA (2007) Limitations of applying summary results of clinical trials to individual patients: the need for risk stratification. JAMA 298(10):1209–1212

    Article  Google Scholar 

  • Kent DM, Alsheikh-Ali A, Hayward RA (2008) Competing risk and heterogeneity of treatment effect in clinical trials. Trials 9:30

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Kwon O, Krishnamoorthy M, Cho YI, Sankovic JM, Banerjee RK (2008) Effect of blood viscosity on oxygen transport in residual stenosed artery following angioplasty. J Biomech Eng 130(1):011003

    Article  Google Scholar 

  • Lee TR, Choi M, Kopacz AM, Yun SH, Liu WK, Decuzzi P (2013) On the near-wall accumulation of injectable particles in the microcirculation: smaller is not better. Sci Rep 3:2079

    Article  Google Scholar 

  • Long M, Zhao H, Huang K-S, Zhu C (2001) Kinetic measurements of cell surface E-selectin/carbohydrate ligand interactions. Ann Biomed Eng 29(11):935–946

    Article  Google Scholar 

  • Maul TM, Dudgeon DD, Beste MT, Hammer DA, Lazo JS, Villanueva FS, Wagner WR (2010) Optimization of ultrasound contrast agents with computational models to improve selection of ligands and binding strength. Biotechnol Bioeng 107(5):854–864

    Article  Google Scholar 

  • Michor F, Liphardt J, Ferrari M, Widom J (2011) What does physics have to do with cancer? Nat Rev Cancer 11(9):657–670

    Article  Google Scholar 

  • Muller K, Fedosov DA, Gompper G (2014) Margination of micro- and nano-particles in blood flow and its effect on drug delivery. Sci Rep 4:4871

    Article  Google Scholar 

  • Muller K, Fedosov DA, Gompper G (2016) Understanding particle margination in blood flow—a step toward optimized drug delivery systems. Med Eng Phys 38(1):2–10

    Article  Google Scholar 

  • MUMPS: MUltifrontal Massively Parallel sparse direct Solver. http://mumps.enseeiht.fr/

  • Muro S, Garnacho C, Champion JA, Leferovich J, Gajewski C, Schuchman EH, Mitragotri S, Muzykantov VR (2008) Control of endothelial targeting and intracellular delivery of therapeutic enzymes by modulating the size and shape of ICAM-1-targeted carriers. Mol Ther 16(8):1450–1458

    Article  Google Scholar 

  • Muzykantov VR (2013) Targeted drug delivery to endothelial adhesion molecules. ISRN Vasc Med 2013:1–27

    Article  Google Scholar 

  • Namdee K, Thompson AJ, Charoenphol P, Eniola-Adefeso O (2013) Margination propensity of vascular-targeted spheres from blood flow in a microfluidic model of human microvessels. Langmuir 29(8):2530–2535

    Article  Google Scholar 

  • Nichols JW, Sakurai Y, Harashima H, Bae YH (2017) Nano-sized drug carriers: extravasation, intratumoral distribution, and their modeling. J Control Release 267:31–46

    Article  Google Scholar 

  • Nie S (2006) Nanotechnology for personalized and predictive medicine. Nanomed Nanotechnol Biol Med. https://doi.org/10.1016/j.nano.2006.10.115

    Article  Google Scholar 

  • Oliveira C, Soares AA, Simões A, Gonzaga S, Rouboa A (2017) Numerical study of non-Newtonian blood behavior in the abdominal aortic bifurcation of a patient-specific at rest. Open Sports Sci J 10(Suppl-2, M9):279–285

    Article  Google Scholar 

  • Sen Gupta A (2016) Role of particle size, shape, and stiffness in design of intravascular drug delivery systems: insights from computations, experiments, and nature. Wiley Interdiscip Rev Nanomed Nanobiotechnol 8(2):255–270

    Article  Google Scholar 

  • Shah PK (2016) Role of inflammation and metalloproteinases in plaque disruption and thrombosis. Vasc Med 3(3):199–206

    Article  Google Scholar 

  • Shamloo A (2014) Cell-cell interactions mediate cytoskeleton organization and collective endothelial cell chemotaxis. Cytoskeleton 71(9):501–512

    Article  Google Scholar 

  • Shamloo A, Manuchehrfar F, Rafii-Tabar H (2015a) A viscoelastic model for axonal microtubule rupture. J Biomech 48(7):1241–1247

    Article  Google Scholar 

  • Shamloo A, Mohammadaliha N, Mohseni M (2015b) Integrative utilization of microenvironments, biomaterials and computational techniques for advanced tissue engineering. J Biotechnol 212:71–89

    Article  Google Scholar 

  • Shamloo A, Mohammadaliha N, Heilshorn SC, Bauer AL (2016) A comparative study of collagen matrix density effect on endothelial sprout formation using experimental and computational approaches. Ann Biomed Eng 44(4):929–941

    Article  Google Scholar 

  • Sohrabi S, Zheng J, Finol EA, Liu Y (2014) Numerical simulation of particle transport and deposition in the pulmonary vasculature. J Biomech Eng 136(12):121010

    Article  Google Scholar 

  • Sohrabi S, Wang S, Tan J, Xu J, Yang J, Liu Y (2017) Nanoparticle transport and delivery in a heterogeneous pulmonary vasculature. J Biomech 50:240–247

    Article  Google Scholar 

  • Tan J, Wang S, Yang J, Liu Y (2013) Coupled particulate and continuum model for nanoparticle targeted delivery. Comput Struct 122:128–134

    Article  Google Scholar 

  • Thompson AJ, Mastria EM, Eniola-Adefeso O (2013) The margination propensity of ellipsoidal micro/nanoparticles to the endothelium in human blood flow. Biomaterials 34(23):5863–5871

    Article  Google Scholar 

  • van der Giessen AG, Groen HC, Doriot PA, de Feyter PJ, van der Steen AF, van de Vosse FN, Wentzel JJ, Gijsen FJ (2011) The influence of boundary conditions on wall shear stress distribution in patients specific coronary trees. J Biomech 44(6):1089–1095

    Article  Google Scholar 

  • Villanueva FS, Lu E, Bowry S, Kilic S, Tom E, Wang J, Gretton J, Pacella JJ, Wagner WR (2007) Myocardial ischemic memory imaging with molecular echocardiography. Circulation 115(3):345–352

    Article  Google Scholar 

  • Vizirianakis IS (2014) Handbook of personalized medicine: advances in nanotechnology, drug delivery, and therapy. Pan Stanford, New York

    Book  Google Scholar 

  • Weinshilboum R (2003) Inheritance and drug response. N Engl J Med 348(6):529–537

    Article  Google Scholar 

  • Weller GE, Villanueva FS, Klibanov AL, Wagner WR (2002) Modulating targeted adhesion of an ultrasound contrast agent to dysfunctional endothelium. Ann Biomed Eng 30(8):1012–1019

    Article  Google Scholar 

  • Weller GE, Lu E, Csikari MM, Klibanov AL, Fischer D, Wagner WR, Villanueva FS (2003) Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted to intercellular adhesion molecule-1. Circulation 108(2):218–224

    Article  Google Scholar 

  • Wu Y, Vendome J, Shapiro L, Ben-Shaul A, Honig B (2011) Transforming binding affinities from three dimensions to two with application to cadherin clustering. Nature 475(7357):510–513

    Article  Google Scholar 

  • Zylberberg C, Matosevic S (2016) Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape. Drug Deliv 23(9):3319–3329

    Article  Google Scholar 

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Acknowledgements

The authors wish to express their thanks to Dr. Amir Sajadieh the interventional cardiologist of the CT-Angio Department of Alzahra Hospital of Isfahan who provided insight and expertise that momentously assisted the research.

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Authors and Affiliations

  1. School of Mechanical Engineering, Sharif University of Technology, Tehran, Iran

    Amir Shamloo

  2. School of Science and Engineering, Sharif University of Technology-International Campus, Kish, Iran

    Mohamadamin Forouzandehmehr

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  1. Amir Shamloo
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  2. Mohamadamin Forouzandehmehr
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Correspondence to Amir Shamloo.

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Shamloo, A., Forouzandehmehr, M. Personalised deposition maps for micro- and nanoparticles targeting an atherosclerotic plaque: attributions to the receptor-mediated adsorption on the inflamed endothelial cells. Biomech Model Mechanobiol 18, 813–828 (2019). https://doi.org/10.1007/s10237-018-01116-y

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