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.

Highlights

  • The first anticancer drug cisplatin (cis-diamminedichloroplatinum(II)) was discovered in 1965 by Rosenberg during his studies on the effects of an electric current on bacterial growth [1]

  • The aim of this study was to investigate the effect of these PtNPs on in vitro amplification of DNA fragment of phage λ, and on the bacterial cultures (Staphylococcus aureus), human foreskin fibroblasts (HFF) and erythrocytes

  • We showed that PtNPs primarily inhibit the activity of Taq DNA polymerase and damage to the DNA structure

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Summary

Introduction

The first anticancer drug cisplatin (cis-diamminedichloroplatinum(II)) was discovered in 1965 by Rosenberg during his studies on the effects of an electric current on bacterial growth [1]. The binding of cisplatin to DNA and the interactions with non-DNA targets with subsequent triggering of cell death through apoptosis, necrosis or both belong to the most important parameters of cisplatin cytotoxicity [2]. Numerous platinum complexes of second generation (carboplatin, oxaliplatin, nedaplatin) and third generation (lobaplatin, heptaplatin) have been developed [3] and evaluated as anticancer agents [4, 5]. Platinum nanoparticles and DNA infrastructure (LM2015043 funded by MEYS CR) for their support with obtaining scientific data presented in this paper

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