SiO₂ nanoparticles as platform for delivery of 3'-triazole analogues of AZT-triphosphate into cells

Bioorg Med Chem. 2015 May 1;23(9):2168-75. doi: 10.1016/j.bmc.2015.02.063. Epub 2015 Mar 7.

Abstract

A system for delivery of analogues of AZT-triphosphates (AZT*TP) based on SiO₂ nanoparticles was proposed. For this purpose, a simple and versatile method was developed for the preparation of SiO₂∼dNTP conjugates using the 'click'-reaction between AZTTP and premodified nanoparticles containing the alkyne groups. The substrate properties of SiO₂∼AZT*TP were tested using Klenow fragment and HIV reverse transcriptase. The 3'-triazole derivatives of thymidine triphosphate being a part of the SiO₂∼AZT*TP nanocomposites were shown to be incorporated into the growing DNA chain. It was shown by confocal microscopy that the proposed SiO₂∼AZT*TP nanocomposites penetrate into cells. These nanocomposites were shown to inhibit the reproduction of POX and Herpes viruses at nontoxic concentrations.

Keywords: 3′-Triazole derivatives of thymidine triphosphates; AZT; Delivery of triphosphate into cells; SiO(2) nanoparticles; Substrate properties; ‘Click’ chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chlorocebus aethiops
  • Click Chemistry
  • Dideoxynucleotides / administration & dosage*
  • Dideoxynucleotides / chemistry*
  • Dideoxynucleotides / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Silicon Dioxide / chemistry*
  • Simplexvirus / drug effects*
  • Simplexvirus / growth & development
  • Structure-Activity Relationship
  • Thymine Nucleotides / administration & dosage*
  • Thymine Nucleotides / chemistry*
  • Thymine Nucleotides / pharmacology
  • Triazoles / chemistry*
  • Variola virus / drug effects*
  • Variola virus / growth & development
  • Vero Cells
  • Zidovudine / administration & dosage
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemistry
  • Zidovudine / pharmacology

Substances

  • Dideoxynucleotides
  • Thymine Nucleotides
  • Triazoles
  • Zidovudine
  • zidovudine triphosphate
  • Silicon Dioxide