A method for the efficient cellular uptake and retention of small modified gold nanoparticles for the radiosensitization of cells

Nanomedicine. 2014 Aug;10(6):1365-73. doi: 10.1016/j.nano.2014.03.011. Epub 2014 Mar 25.

Abstract

Gold nanoparticles (GNP) enhance the absorbance of photons thereby increasing emission of Auger-/photoelectrons in the nm-μm range. Yet, a major disadvantage is their diameter-dependent cellular uptake with an optimum of ~50 nm which may not offer optimal radiosensitization. A method was developed to enhance the uptake of small GNP. GNP (10nm) were linked to DNA and transferred into HeLa cells by transient transfection (GNP-DT). Treatment of cells with GNP-DT resulted in a strong perinuclear focal accumulation, whereas this was dimmer and sparser for GNP-T (lacking DNA) and close to background levels in GNP-treated cells. Only GNP-DT showed a significant radiosensitizing effect (p=0.005) on clonogenic survival using clinically relevant megavolt x-rays. Our novel method markedly increases the uptake/retention and alters the localization of small GNP in cells compared to unmodified GNP. This work finally enables studying the radiosensitizing effects of differentially sized GNP.

From the clinical editor: In an effort to increase the radiosensitization of HeLa cells, his paper discusses a transient transfection-based method to enhance gold nanoparticle intracellular delivery.

Keywords: Auger electrons; Gold nanoparticles; Radiosensitization; Size dependency; Transfection; Uptake.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry
  • DNA / genetics
  • Gold / administration & dosage*
  • Gold / chemistry
  • Gold / pharmacokinetics
  • HeLa Cells
  • Humans
  • Metal Nanoparticles / administration & dosage*
  • Particle Size
  • Radiation-Sensitizing Agents / administration & dosage*
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / pharmacokinetics
  • Transfection*

Substances

  • Radiation-Sensitizing Agents
  • Gold
  • DNA