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Relief from vascular occlusion using photothermal ablation of thrombus with a multimodal perspective


Fibrinolytic therapy for arterial or venous thrombotic disorders involves the systemic administration of thrombolytics such as streptokinase, which is associated with serious bleeding complications. With this study, we provide a proof-of-concept of photothermal thrombus ablation with gold nanorods exposed to near-infrared irradiation, both in vitro using materials generated from purified fibrinogen or plasma and in vivo in murine blood vessels. This is the first report of the application of photothermal therapy as an anti-thrombotic measure. Remarkably, the addition of streptokinase had a multimodal additive effect with regard to acceleration of photothermal lysis of thrombi even at a dose significantly below the therapeutic concentration, thus minimizing the life-threatening side effects and adverse complications. This combinatorial approach exhibits great promise for lysing pathological clots while effectively overcoming the drawbacks of existing therapies.

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  1. [1]

    Canto, J. G.; Rogers, W. J.; Goldberg, R. J.; Peterson, E. D.; Wenger, N. K.; Vaccarino, V.; Kiefe, C. I.; Frederick, P. D.; Sopko, G.; Zheng, Z.-J. et al. Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality. JAMA 2012, 307, 813–822.

    Google Scholar 

  2. [2]

    Weitz, J. I. Antiplatelet, anticoagulant, and fibrinolytic drugs. In Harrison’s Principles of Internal Medicine. Longo, D. L.; Fauci, A. S.; Kasper, D. L.; Hauser, S. L.; Jameson, J. L.; Loscalzo, J., Eds.; McGraw-Hill: New Delhi, 2011; Vol. 1, pp 1001–1003.

    Google Scholar 

  3. [3]

    Tsai, M. F.; Chang, S. H. G.; Cheng, F. Y.; Shanmugam, V.; Cheng, Y. S.; Su, C. H.; Yeh, C. S. Au nanorod design as light-absorber in the first and second biological near-infrared windows for in vivo photothermal therapy. ACS Nano 2013, 7, 5330–5342.

    Article  Google Scholar 

  4. [4]

    Mosesson, M. W. Fibrinogen and fibrin structure and functions. J. Thromb. Haemost. 2005, 3, 1894–1904.

    Article  Google Scholar 

  5. [5]

    Hethershaw, E. L.; Cilia La Corte, A. L.; Duval, C.; Ali, M.; Grant, P. J.; Ariëns, R. A. S.; Philippou, H. The effect of blood coagulation factor XIII on fibrin clot structure and fibrinolysis. J. Thromb. Haemost. 2014, 12, 197–205.

    Article  Google Scholar 

  6. [6]

    Chernysh, I. N.; Everbach, C. E.; Purohit, P. K.; Weisel, J. W. Molecular mechanisms of the effect of ultrasound on the fibrinolysis of clots. J. Thromb. Haemost. 2015, 13, 601–609.

    Article  Google Scholar 

  7. [7]

    Walters, M. I. An evaluation of hemoglobin concentrations obtained with frozen altered Drabkin’s reagents. Clin. Chem. 1968, 14, 682–691.

    Google Scholar 

  8. [8]

    Chernysh, I. N.; Nagaswami, C.; Purohit, P. K.; Weisel, J. W. Fibrin clots are equilibrium polymers that can be remodeled without proteolytic digestion. Sci. Rep. 2012, 2, 879.

    Article  Google Scholar 

  9. [9]

    Gersh, K. C.; Zaitsev, S.; Cines, D. B.; Muzykantov, V.; Weisel, J. W. Flow-dependent channel formation in clots by an erythrocyte-bound fibrinolytic agent. Blood 2011, 117, 4964–4967.

    Article  Google Scholar 

  10. [10]

    Westrick, R. J.; Winn, M. E.; Eitzman, D. T. Murine models of vascular thrombosis. Arterioscler. Thromb. Vasc. Biol. 2007, 27, 2079–2093.

    Article  Google Scholar 

  11. [11]

    Liopo, A.; Conjusteau, A.; Tsyboulski, D.; Ermolinsky, B.; Kazansky, A.; Oraevsky, A. Biocompatible gold nanorod conjugates for preclinical biomedical research. J. Nanomed. Nanotechnol. 2012, 6, 274.

    Google Scholar 

  12. [12]

    Falati, S.; Gross, P.; Merrill-Skoloff, G.; Furie, B. C.; Furie, B. Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse. Nat. Med. 2002, 8, 1175–1180.

    Article  Google Scholar 

  13. [13]

    Nagai, N.; Vanlinthout, I.; Collen, D. Comparative effects of tissue plasminogen activator, streptokinase, and staphylokinase on cerebral ischemic infarction and pulmonary clot lysis in hamster models. Circulation 1999, 100, 2541–2546.

    Article  Google Scholar 

  14. [14]

    Small, W.; Wilson, T. S.; Benett, W. J.; Loge, J. M.; Maitland, D. J. Laser-activated shape memory polymer intravascular thrombectomy device. Opt. Express 2005, 13, 8204–8213.

    Article  Google Scholar 

  15. [15]

    Kuo, W. T.; Odegaard, J. I.; Louie, J. D.; Sze, D. Y.; Unver, K.; Kothary, N.; Rosenberg, J. K.; Hovesepian, D. M.; Hwang, G. L.; Hofmann, L. V. Photothermal ablation with the excimer laser sheath technique for embedded inferior vena cava filter removal: Initial results from a prospective study. J. Vasc. Interv. Radiol. 2011, 22, 813–823.

    Article  Google Scholar 

  16. [16]

    Kharlamov, A. N.; Gabinsky, J. L. Plasmonic photothermic and stem cell therapy of atherosclerotic plaque as a novel nanotool for angioplasty and artery remodeling. Rejuvenation Res. 2012, 15, 222–230.

    Article  Google Scholar 

  17. [17]

    Walker, J. M.; Zaleski, J. M. Non-enzymatic remodeling of fibrin biopolymers via photothermally triggered radicalgenerating nanoparticles. Chem. Mater. 2014, 26, 5120–5130.

    Article  Google Scholar 

  18. [18]

    Choi, J.; Yang, J.; Jang, E.; Suh, J. S.; Huh, Y. M.; Lee, K.; Haam, S. Gold nanostructures as photothermal therapy agent for cancer. Anti-Cancer Agents Med. Chem. 2011, 11, 953–964.

    Article  Google Scholar 

  19. [19]

    Green, H. N.; Martyshkin, D. V.; Rodenburg, C. M.; Rosenthal, E. L.; Mirov, S. B. Gold nanorod bioconjugates for active tumor targeting and photothermal therapy. J. Nanotechnol. 2011, 2011, Article ID 631753.

    Google Scholar 

  20. [20]

    Gaffney, P. J.; Whitaker, A. N. Fibrin crosslinks and lysis rates. Thromb. Res. 1979, 14, 85–94.

    Article  Google Scholar 

  21. [21]

    McDonagh Jr, R. P.; McDonagh, J.; Duckert, F. The influence of fibrin crosslinking on the kinetics of urokinase-induced clot lysis. Br. J. Haematol. 1971, 21, 323–332.

    Article  Google Scholar 

  22. [22]

    Banerjee, A.; Chisti, Y.; Banerjee, U. C. Streptokinase—A clinically useful thrombolytic agent. Biotechnol. Adv. 2004, 22, 287–307.

    Article  Google Scholar 

  23. [23]

    Collen, D.; de Cock, F.; Stassen, J. M. Comparative immunogenicity and thrombolytic properties toward arterial and venous thrombi of streptokinase and recombinant staphylokinase in baboons. Circulation 1993, 87, 996–1006.

    Article  Google Scholar 

  24. [24]

    Betancourt, B. Y.; Marrero-Miragaya, M. A.; Jiménez-López, G.; Valenzuela-Silva, C.; García-Iglesias, E.; Hernández-Bernal, F.; Debesa-García, F.; González-López, T.; Alvarez-Falcón, L.; López-Saura, P. A. et al. Pharmacovigilance program to monitor adverse reactions of recombinant streptokinase in acute myocardial infarction. BMC Clin. Pharmacol. 2005, 5, 5.

    Article  Google Scholar 

  25. [25]

    Kunitada, S.; FitzGerald, G. A.; Fitzgerald, D. J. Inhibition of clot lysis and decreased binding of tissue-type plasminogen activator as a consequence of clot retraction. Blood 1992, 79, 1420–1427.

    Google Scholar 

  26. [26]

    Katori, N.; Tanaka, K. A.; Szlam, F.; Levy, J. H. The effects of platelet count on clot retraction and tissue plasminogen activator-induced fibrinolysis on thrombelastography. Anesth. Analg. 2005, 100, 1781–1785.

    Article  Google Scholar 

  27. [27]

    Leung, J. P.; Wu, S.; Chou, K. C.; Signorell, R. Investigation of sub-100 nm gold nanoparticles for laser-induced thermotherapy of cancer. Nanomaterials 2013, 3, 86–106.

    Article  Google Scholar 

  28. [28]

    Kennedy, L. C.; Bickford, L. R.; Lewinski, N. A.; Coughlin, A. J.; Hu, Y.; Day, E. S.; West, J. L.; Drezek, R. A. A new era for cancer treatment: Gold-nanoparticle-mediated thermal therapies. Small 2011, 7, 169–183.

    Article  Google Scholar 

  29. [29]

    Dickerson, E. B.; Dreaden, E. C.; Huang, X. H.; El-Sayed, I. H.; Chu, H. H.; Pushpanketh, S.; McDonald, J. F.; El-Sayed, M. A. Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice. Cancer Lett. 2008, 269, 57–66.

    Article  Google Scholar 

  30. [30]

    Rengan, A. K.; Bukhari, A. B.; Pradhan, A.; Malhotra, R.; Banerjee, R.; Srivastava, R.; De, A. In vivo analysis of biodegradable liposome gold nanoparticles as efficient agents for photothermal therapy of cancer. Nano Lett. 2015, 15, 842–848.

    Article  Google Scholar 

  31. [31]

    Hudson, D. E.; Hudson, D. O.; Wininger, J. M.; Richardson, B. D. Penetration of laser light at 808 and 980 nm in bovine tssue samples. Photomed. Laser Surg. 2013, 31, 163–168.

    Article  Google Scholar 

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Correspondence to Debabrata Dash.

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These authors contributed equally to this work.

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Singh, N., Varma, A., Verma, A. et al. Relief from vascular occlusion using photothermal ablation of thrombus with a multimodal perspective. Nano Res. 9, 2327–2337 (2016).

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  • platelet
  • fibrin
  • near-infrared laser
  • photothermal therapy
  • thrombolysis
  • streptokinase