Design and synthesis of nanoscaled IQCA-TAVV as a delivery system capable of antiplatelet activation, targeting arterial thrombus and releasing IQCA

Background Arterial thrombosis has been associated with a series of pathological conditions, and the discovery of arterial thrombosis inhibitor is of clinical importance. Methods By analyzing the pharmacophores of anti-platelet agents, thrombus targeting peptide and anti-thrombotic nano-systems 3S-1,2,3,4-tetrahydroisoquino-line-3-carbonyl-Thr-Ala-Arg-Gly-Asp(Val)-Val (IQCA-TAVV) was designed and prepared as a nano-scaled arterial thrombosis inhibitor. Results In vitro the nanoparticles of IQCA-TAVV were able to adhere onto the surface of activated platelets, attenuate activated platelets to extend pseudopodia and inhibit activated platelets to form aggregators. In vivo IQCA-TAVV targeted arterial thrombus, dose dependently inhibited arterial thrombosis with a 1 nmol/kg of minimal effective dose, and the activity waŝ1670 folds of that of aspirin. Conclusion IQCA-TAVV represented the design, preparation and application of nanomedicine capable of adhering on the surface of activated platelets, attenuating platelet activation, targeting arterial thrombus and inhibiting arterial thrombosis.

[1]  R. Koehler,et al.  Inhibition of tPA-induced hemorrhagic transformation involves adenosine A2b receptor activation after cerebral ischemia , 2017, Neurobiology of Disease.

[2]  G. Tae,et al.  In situ formation of injectable and porous heparin-based hydrogel. , 2017, Carbohydrate polymers.

[3]  B. Payrastre,et al.  The importance of blood platelet lipid signaling in thrombosis and in sepsis. , 2017, Advances in biological regulation.

[4]  V. Bazan,et al.  Galectin-3 in acute coronary syndrome. , 2017, Clinical biochemistry.

[5]  J. Arnaez,et al.  Extracerebral thrombosis in symptomatic neonatal arterial ischemic stroke. , 2017, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[6]  U. Desai,et al.  Heparin depolymerization by immobilized heparinase: A review. , 2017, International journal of biological macromolecules.

[7]  J. Truong,et al.  Superior mesenteric artery thrombosis , 2017 .

[8]  P. Ryan,et al.  Risk Prediction for Ischemic Stroke and Transient Ischemic Attack in Patients Without Atrial Fibrillation: A Retrospective Cohort Study. , 2017, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[9]  J. Rankin,et al.  Late Strut Fracture Within a Partially Resorbed Bioresorbable Vascular Scaffold: A Possible Cause of Late Scaffold Thrombosis and Acute Coronary Syndrome. , 2017, Heart, lung & circulation.

[10]  E. Wirrell,et al.  Epidemiology and Outcomes of Arterial Ischemic Stroke in Children: The Canadian Pediatric Ischemic Stroke Registry. , 2017, Pediatric neurology.

[11]  Ming Zhao,et al.  IQCA-TASS: a nano-scaled P-selectin inhibitor capable of targeting thrombus and releasing IQCA/TARGD(S)S in vivo. , 2017, Journal of materials chemistry. B.

[12]  Y. Zhang,et al.  Metabolic syndrome and its individual components with mortality among patients with coronary heart disease. , 2016, International journal of cardiology.

[13]  W. J. van der Spuy,et al.  Ultrastructural investigation of the time-dependent relationship between breast cancer cells and thrombosis induction. , 2016, Micron.

[14]  Ahmed Sayed Ahmed Elsayed,et al.  Satisfaction with and adherence to warfarin treatment: A cross-sectional study among Sudanese patients , 2016, Journal of the Saudi Heart Association.

[15]  P. Morange,et al.  Potential mechanism of acute stent thrombosis with bivalirudin following percutaneous coronary intervention in acute coronary syndromes. , 2016, International journal of cardiology.

[16]  G. Hasenfuss,et al.  CCL5 deficiency reduces neointima formation following arterial injury and thrombosis in apolipoprotein E-deficient mice. , 2016, Thrombosis research.

[17]  M. Carrington,et al.  A metabolic syndrome severity score: A tool to quantify cardio-metabolic risk factors. , 2016, Preventive medicine.

[18]  L. O’Driscoll,et al.  Blood-Based Biomarkers for Metabolic Syndrome , 2016, Trends in Endocrinology & Metabolism.

[19]  J. Harenberg Past, present, and future perspectives of heparins in clinical settings and the role of impaired renal function. , 2016, International journal of cardiology.

[20]  B. Nilsson,et al.  Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions. , 2016, Colloids and surfaces. B, Biointerfaces.

[21]  G. Castaman Risk of thrombosis in cancer and the role of supportive care (transfusion, catheters, and growth factors). , 2016, Thrombosis research.

[22]  N. Funabashi,et al.  Combined ostium secundum type ASD and pulmonary arterial thromboembolism causing pulmonary artery enlargement, pulmonary hypertension and recurrent paradoxical cerebral embolism due to deep venous thrombosis. , 2016, International journal of cardiology.

[23]  E. Conway,et al.  Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin , 2016, EBioMedicine.

[24]  M. MacConmara,et al.  Increased risk of vascular thrombosis in pediatric liver transplant recipients with thrombophilia. , 2015, The Journal of surgical research.

[25]  Y. Morishima,et al.  Paradoxical enhancement of the intrinsic pathway-induced thrombin generation in human plasma by melagatran, a direct thrombin inhibitor, but not edoxaban, a direct factor Xa inhibitor, or heparin. , 2015, Thrombosis research.

[26]  O. Kamp,et al.  Therapeutic application of contrast-enhanced ultrasound and low-dose urokinase for thrombolysis in a porcine model of acute peripheral arterial occlusion. , 2015, Journal of vascular surgery.

[27]  J. Piette,et al.  Safety and efficacy of oral direct inhibitors of thrombin and factor Xa in antiphospholipid syndrome. , 2015, Autoimmunity reviews.

[28]  Viola Macolic Sarinic,et al.  Clinical Application of Genotype-guided Dosing of Warfarin in Patients with Acute Stroke. , 2015, Archives of medical research.

[29]  S. Umemura,et al.  Effect of impaired renal function on the maintenance dose of warfarin in Japanese patients. , 2015, Journal of cardiology.

[30]  Sang-Hyun Kim,et al.  The effects of metabolic syndrome and its components on arterial stiffness in relation to gender. , 2015, Journal of cardiology.

[31]  Seung-Yeon Cho,et al.  Safety of acupuncture treatments for patients taking warfarin or antiplatelet medications: Retrospective chart review study , 2014 .

[32]  Ming Zhao,et al.  Nanosized aspirin-Arg-Gly-Asp-Val: delivery of aspirin to thrombus by the target carrier Arg-Gly-Asp-Val tetrapeptide. , 2013, ACS nano.

[33]  M. Schindewolf,et al.  High incidence of heparin-induced allergic delayed-type hypersensitivity reactions in pregnancy. , 2013, The Journal of allergy and clinical immunology.

[34]  Haiqiang Jin,et al.  Ultrasound-triggered thrombolysis using urokinase-loaded nanogels. , 2012, International journal of pharmaceutics.

[35]  Ming Zhao,et al.  The application of tetrahydroisoquinoline-3-carbonyl-TARGD(F)F as an anti-thrombotic agent having dual mechanisms of action. , 2012, Molecular bioSystems.

[36]  C. Ali,et al.  tPA in the injured central nervous system: different scenarios starring the same actor? , 2012, Neuropharmacology.

[37]  Anwar Rayan,et al.  Blood–brain barrier permeability and tPA-mediated neurotoxicity , 2010, Neuropharmacology.

[38]  Ming Zhao,et al.  A class of novel N-(3S-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-L-amino acid derivatives: their synthesis, anti-thrombotic activity evaluation, and 3D QSAR analysis. , 2009, European journal of medicinal chemistry.

[39]  Jing Zhang,et al.  Chemical conjugation of urokinase to magnetic nanoparticles for targeted thrombolysis. , 2009, Biomaterials.

[40]  Junling Liu,et al.  Palladin is involved in platelet activation and arterial thrombosis. , 2017, Thrombosis research.

[41]  M. Rodríguez-Zúñiga,et al.  Association of Psoriasis and Metabolic Syndrome in Latin America: A Systematic Review and Meta-Analysis. , 2017, Actas dermo-sifiliograficas.