Design and Synthesis of Nanoscaled IQCA-TAVV As a Delivery System Capable of Antiplatelet Activation, Targeting Arterial Thrombus and Releasing IQCA

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2018 Mar 10

PMID 29520141

Citations 8

Authors

Jianhui Wu

Haimei Zhu

Guodong Yang

Jianhong He

Yuji Wang

Shurui Zhao

Xiaoyi Zhang

Lin Gui

Ming Zhao

Shiqi Peng

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Advances in drug delivery systems utilizing blood cells and their membrane-derived microvesicles.

He A, Huang Y, Cao C, Li X Drug Deliv. 2024; 31(1):2425156.

PMID: 39520082 PMC: 11552282. DOI: 10.1080/10717544.2024.2425156.

Nanosystems in Cardiovascular Medicine: Advancements, Applications, and Future Perspectives.

Omidian H, Babanejad N, Cubeddu L Pharmaceutics. 2023; 15(7).

PMID: 37514121 PMC: 10386572. DOI: 10.3390/pharmaceutics15071935.

Nanobiotechnology approaches for cardiovascular diseases: site-specific targeting of drugs and nanoparticles for atherothrombosis.

Liu H, Pietersz G, Peter K, Wang X J Nanobiotechnology. 2022; 20(1):75.

PMID: 35135581 PMC: 8822797. DOI: 10.1186/s12951-022-01279-y.

Nanoparticles of a New Small-Molecule P-Selectin Inhibitor Attenuate Thrombosis, Inflammation, and Tumor Growth in Two Animal Models.

Feng Q, Wang M, Muhtar E, Wang Y, Zhu H Int J Nanomedicine. 2021; 16:5777-5795.

PMID: 34471352 PMC: 8403725. DOI: 10.2147/IJN.S316863.

discovery of SARS-CoV-2 main protease inhibitors from the carboline and quinoline database.

Muhtar E, Wang M, Zhu H Future Virol. 2021; .

PMID: 34306166 PMC: 8293686. DOI: 10.2217/fvl-2021-0099.

References

van der Spuy W, Augustine T . Ultrastructural investigation of the time-dependent relationship between breast cancer cells and thrombosis induction. Micron. 2016; 90:59-63. DOI: 10.1016/j.micron.2016.08.006. View

Funabashi N, Takaoka H, Ozawa K, Tanabe N, Tatsumi K, Saeki N . 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. Int J Cardiol. 2016; 207:303-7. DOI: 10.1016/j.ijcard.2016.01.178. View

Chen X, Fan X, Tan J, Shi P, Wang X, Wang J . Palladin is involved in platelet activation and arterial thrombosis. Thromb Res. 2016; 149:1-8. DOI: 10.1016/j.thromres.2016.11.010. View

Castaman G . Risk of thrombosis in cancer and the role of supportive care (transfusion, catheters, and growth factors). Thromb Res. 2016; 140 Suppl 1:S89-92. DOI: 10.1016/S0049-3848(16)30105-0. View

Foley J, Walton B, Aleman M, OByrne A, Lei V, Harrasser M . Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin. EBioMedicine. 2016; 5:175-82. PMC: 4816834. DOI: 10.1016/j.ebiom.2016.02.011. View

Yang G, Zhu H, Zhao M, Wu J, Wang Y, Wang Y . The application of tetrahydroisoquinoline-3-carbonyl-TARGD(F)F as an anti-thrombotic agent having dual mechanisms of action. Mol Biosyst. 2012; 8(10):2672-9. DOI: 10.1039/c2mb25112d. View

Rodriguez-Zuniga M, Cortez-Franco F, Quijano-Gomero E . Association of Psoriasis and Metabolic Syndrome in Latin America: A Systematic Review and Meta-Analysis. Actas Dermosifiliogr. 2017; 108(4):326-334. DOI: 10.1016/j.ad.2016.11.009. View

Schindewolf M, Gobst C, Kroll H, Recke A, Louwen F, Wolter M . High incidence of heparin-induced allergic delayed-type hypersensitivity reactions in pregnancy. J Allergy Clin Immunol. 2013; 132(1):131-9. DOI: 10.1016/j.jaci.2013.02.047. View

ONeill S, Bohl M, Gregersen S, Hermansen K, ODriscoll L . Blood-Based Biomarkers for Metabolic Syndrome. Trends Endocrinol Metab. 2016; 27(6):363-374. DOI: 10.1016/j.tem.2016.03.012. View

10.

Jin H, Tan H, Zhao L, Sun W, Zhu L, Sun Y . Ultrasound-triggered thrombolysis using urokinase-loaded nanogels. Int J Pharm. 2012; 434(1-2):384-90. DOI: 10.1016/j.ijpharm.2012.06.001. View

11.

Kim H, Lee J, Seo J, Chung W, Kim S, Zo J . The effects of metabolic syndrome and its components on arterial stiffness in relation to gender. J Cardiol. 2014; 65(3):243-9. DOI: 10.1016/j.jjcc.2014.05.009. View

12.

Agnello L, Bivona G, Lo Sasso B, Scazzone C, Bazan V, Bellia C . Galectin-3 in acute coronary syndrome. Clin Biochem. 2017; 50(13-14):797-803. DOI: 10.1016/j.clinbiochem.2017.04.018. View

13.

Yuan Z, Voss E, Defalco F, Pan G, Ryan P, Yannicelli D . Risk Prediction for Ischemic Stroke and Transient Ischemic Attack in Patients Without Atrial Fibrillation: A Retrospective Cohort Study. J Stroke Cerebrovasc Dis. 2017; 26(8):1721-1731. DOI: 10.1016/j.jstrokecerebrovasdis.2017.03.036. View

14.

Cheng S, Zhang X, Wang W, Zhao M, Zheng M, Chang H . 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. Eur J Med Chem. 2009; 44(12):4904-19. DOI: 10.1016/j.ejmech.2009.08.002. View

15.

Cha D, Alfrey E, Desai D, MacConmara M, Hwang C . Increased risk of vascular thrombosis in pediatric liver transplant recipients with thrombophilia. J Surg Res. 2015; 199(2):671-5. DOI: 10.1016/j.jss.2015.07.043. View

16.

Ichihara N, Ishigami T, Umemura S . Effect of impaired renal function on the maintenance dose of warfarin in Japanese patients. J Cardiol. 2014; 65(3):178-84. DOI: 10.1016/j.jjcc.2014.08.008. View

17.

Wiley J, Carrington M . A metabolic syndrome severity score: A tool to quantify cardio-metabolic risk factors. Prev Med. 2016; 88:189-95. DOI: 10.1016/j.ypmed.2016.04.006. View

18.

Goh M, Kim Y, Gwon K, Min K, Hwang Y, Tae G . In situ formation of injectable and porous heparin-based hydrogel. Carbohydr Polym. 2017; 174:990-998. DOI: 10.1016/j.carbpol.2017.06.126. View

19.

Laine M, Frere C, Cuisset T, Paganelli F, Morange P, Dignat-George F . Potential mechanism of acute stent thrombosis with bivalirudin following percutaneous coronary intervention in acute coronary syndromes. Int J Cardiol. 2016; 220:496-500. DOI: 10.1016/j.ijcard.2016.06.247. View

20.

Bounes F, Mujalli A, Cenac C, Severin S, Le Faouder P, Chicanne G . The importance of blood platelet lipid signaling in thrombosis and in sepsis. Adv Biol Regul. 2017; 67:66-73. DOI: 10.1016/j.jbior.2017.09.011. View