FePt-Cys nanoparticles induce ROS-dependent cell toxicity, and enhance chemo-radiation sensitivity of NSCLC cells in vivo and in vitro

Cancer Lett. 2018 Apr 1:418:27-40. doi: 10.1016/j.canlet.2018.01.024. Epub 2018 Jan 11.

Abstract

FePt-Cys nanoparticles (FePt-Cys NPs) have been well used in many fields, despite their poor solubility and stability. We synthetized a cysteine surface modified FePt NPs, which exhibited good solubility, stability and biocompatibility. We explored the insight mechanisms of the antitumor effects of this new nanoparticle system in lung cancer cells. In the in vitro study, FePt-Cys NPs induced a reactive oxygen species (ROS) burst, which suppressed the antioxidant protein expression and induced cell apoptosis. Furthermore, FePt-Cys NPs prevented the migration and invasion of H1975 and A549 cells. These changes were correlated with a dramatic decrease in MMP-2/9 expression and enhanced the cellular attachment. We demonstrated that FePt-Cys NPs promoted the effects of chemo-radiation through activation of the caspase system and impairment of DNA damage repair. In the in vivo study, no severe allergies or drug-related deaths were observed and FePt-Cys NPs showed a synergistic effect with cisplatin and radiation. In conclusion, with good safety and efficacy, FePt-Cys NPs could therefore be potential sensitizers for chemoradiotherapy.

Keywords: Chemo-radiation sensitivity; FePt-Cys nanoparticles; ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chemoradiotherapy
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Cysteine / chemistry
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Magnetite Nanoparticles / administration & dosage*
  • Magnetite Nanoparticles / chemistry
  • Platinum / chemistry
  • Reactive Oxygen Species / metabolism*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Magnetite Nanoparticles
  • Reactive Oxygen Species
  • Platinum
  • Cysteine
  • Cisplatin