Smart bomb AS1411 aptamer-functionalized/PAMAM dendrimer nanocarriers for targeted drug delivery in the treatment of gastric cancer

Clin Exp Pharmacol Physiol. 2017 Jan;44(1):41-51. doi: 10.1111/1440-1681.12670.

Abstract

Chemotherapy, a conventional method assessed in recent oncology studies, poses numerous problems in the clinical environment. To overcome the problems inherent in chemotherapy, an intelligent drug delivery system has come to the forefront of cancer therapeutics. In this study, we designed a dendrimer-based pharmaceutical system together with a single-stranded AS1411 aptamer (APTAS1411 ) as a therapeutic strategy. The polyamidoamine (PAMAM)-polyethylene glycol (PEG) complex was then conjugated with the AS1411 aptamer and confirmed by atomic-force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) .In this study, we show that the conjugated PAMAM-PEG-APTAS1411 complex dramatically increased PAMAM-PEG-5-FU uptake by MKN45 gastric cancer cells. We also demonstrated both the stability of the nanoparticle-5-FU-APTAS1411 complex, by thin layer chromatography (TLC), and an increase in 5-fluorouracil (5-FU) accumulation in the vicinity of cancerous tumors. This smart drug delivery system is capable of effectively transferring 5-FU to MKN45 gastric cancer cells in consistent and without toxic effects.

Keywords: 5-fluorouracil; PAMAM; aptamer; drug delivery; nucleolin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aptamers, Nucleotide / administration & dosage*
  • Aptamers, Nucleotide / metabolism
  • Cell Line, Tumor
  • Dendrimers / administration & dosage*
  • Dendrimers / metabolism
  • Drug Carriers / administration & dosage
  • Drug Carriers / metabolism
  • Drug Delivery Systems / methods*
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Nanoparticles / metabolism
  • Oligodeoxyribonucleotides / administration & dosage*
  • Oligodeoxyribonucleotides / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Treatment Outcome
  • Xenograft Model Antitumor Assays / methods

Substances

  • AGRO 100
  • Aptamers, Nucleotide
  • Dendrimers
  • Drug Carriers
  • Oligodeoxyribonucleotides
  • PAMAM Starburst