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

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.

• Authors: Jianhui Wu, Haimei Zhu, Guodong Yang, Jianhong He, Yuji Wang, Shurui Zhao, Xiaoyi Zhang, Lin Gui, Ming Zhao, Shiqi Peng
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 13 Pg. 1139-1158 ( 2018) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 29520141 (Publication Type: Journal Article)

Chemical References

• Oligopeptides
• Platelet Aggregation Inhibitors
• arginyl-glycyl-aspartyl-alanine
• Aspirin

Topics

• Animals
• Aspirin (pharmacology)
• Blood Platelets (drug effects, ultrastructure)
• Carotid Arteries (drug effects, pathology)
• Dimerization
• Drug Delivery Systems
• Drug Design
• Fourier Analysis
• Humans
• Magnetic Resonance Spectroscopy
• Male
• Mass Spectrometry
• Mice
• Microscopy, Atomic Force
• Molecular Conformation
• Nanoparticles (chemistry, ultrastructure)
• Oligopeptides (chemical synthesis, chemistry)
• Platelet Activation (drug effects)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Rats, Sprague-Dawley
• Static Electricity
• Sus scrofa
• Thrombosis (blood, drug therapy, pathology)