Platinum nanoparticles induce damage to DNA and inhibit DNA replication

PLoS One. 2017 Jul 12;12(7):e0180798. doi: 10.1371/journal.pone.0180798. eCollection 2017.

Abstract

Sparsely tested group of platinum nanoparticles (PtNPs) may have a comparable effect as complex platinum compounds. The aim of this study was to observe the effect of PtNPs in in vitro amplification of DNA fragment of phage λ, on the bacterial cultures (Staphylococcus aureus), human foreskin fibroblasts and erythrocytes. In vitro synthesized PtNPs were characterized by dynamic light scattering (PtNPs size range 4.8-11.7 nm), zeta potential measurements (-15 mV at pH 7.4), X-ray fluorescence, UV/vis spectrophotometry and atomic absorption spectrometry. The PtNPs inhibited the DNA replication and affected the secondary structure of DNA at higher concentrations, which was confirmed by polymerase chain reaction, DNA sequencing and DNA denaturation experiments. Further, cisplatin (CisPt), as traditional chemotherapy agent, was used in all parallel experiments. Moreover, the encapsulation of PtNPs in liposomes (LipoPtNPs) caused an approximately 2.4x higher of DNA damage in comparison with CisPt, LipoCisPt and PtNPs. The encapsulation of PtNPs in liposomes also increased their antibacterial, cytostatic and cytotoxic effect, which was determined by the method of growth curves on S. aureus and HFF cells. In addition, both the bare and encapsulated PtNPs caused lower oxidative stress (determined by GSH/GSSG ratio) in the human erythrocytes compared to the bare and encapsulated CisPt. CisPt was used in all parallel experiments as traditional chemotherapy agent.

MeSH terms

  • Cell Line
  • Cells, Cultured
  • DNA Damage*
  • DNA Replication*
  • Erythrocytes / drug effects
  • Fibroblasts / drug effects
  • Humans
  • Metal Nanoparticles / adverse effects*
  • Metal Nanoparticles / chemistry
  • Oxidative Stress
  • Platinum / adverse effects
  • Platinum / chemistry
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics

Substances

  • Platinum

Grants and funding

This research was carried out under the project CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II. The financial support from AZV project no. 15-28334A is also highly acknowledged. Moreover, authors acknowledge the CF CEITEC - Cryo-electron Microscopy and Tomography supported by the CIISB research infrastructure (LM2015043 funded by MEYS CR) for their support with obtaining scientific data presented in this paper.