Nano-scaled MTCA-KKV: for targeting thrombus, releasing pharmacophores, inhibiting thrombosis and dissolving blood clots in vivo

Int J Nanomedicine. 2019 Jul 3:14:4817-4831. doi: 10.2147/IJN.S206294. eCollection 2019.

Abstract

Background: In vitro (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxyl-Lys(Pro-Ala-Lys)-Arg-Gly-Asp-Val (MTCA-KKV) adheres activated platelets, targets P-selectin and GPIIb/IIIa. This led to the development of MTCA-KKV as thrombus targeting nano-medicine.

Methods: MTCA-KKV was characterized by nano-feature, anti-thrombotic activity, thrombolytic activity, thrombus target and targeting release.

Results: In vivo 0.01 μmol/kg of MTCA-KKV formed nano-particles less than 100 nm in diameter, targeted thrombus, released anti-thrombotic and thrombolytic pharmacophores, prevented thrombosis and dissolved blood clots.

Conclusion: Based on the profiles of targeting thrombus, targeting release, inhibiting thrombosis and dissolving blood clots MTCA-KKV is a promising nano-medicine.

Keywords: anti-thrombotic; nano-particles; release; targeting; thrombolytic.

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Coagulation* / drug effects
  • Blood Platelets / drug effects
  • Carbolines / administration & dosage
  • Carbolines / chemistry*
  • Carbolines / therapeutic use*
  • Erythrocytes / drug effects
  • Humans
  • Leukocytes / drug effects
  • Magnetic Resonance Spectroscopy
  • Male
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • P-Selectin / metabolism
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Platelet Adhesiveness / drug effects
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Rats, Sprague-Dawley
  • Spectroscopy, Fourier Transform Infrared
  • Thrombosis / blood*
  • Thrombosis / drug therapy*

Substances

  • Carbolines
  • P-Selectin
  • Peptides
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid