Iron-gold alloy nanoparticles serve as a cornerstone in hyperthermia-mediated controlled drug release for cancer therapy

Int J Nanomedicine. 2018 Sep 17:13:5499-5509. doi: 10.2147/IJN.S163721. eCollection 2018.

Abstract

Introduction: The efficacy of a chemotherapy drug in cancer therapy is highly determined by the ability to control the rate and extent of its release in vivo. However, the lack of techniques to accurately control drug release drastically limits the potency of a chemotherapy drug.

Materials and methods: Here, we present a novel strategy to precisely monitor drug release under magnetic stimulation. Methotrexate (MTX), an anticancer drug, was covalently functionalized onto iron-gold alloy magnetic nanoparticles (Fe-Au alloy nanoparticles or NFAs) through 2-aminoethanethiol grafting and the ability of this drug-nanoparticle conjugate (NFA-MTX) in limiting HepG2 (liver carcinoma) cell growth was studied. Well-dispersed NFAs were prepared through pyrolysis.

Results and discussion: Transmission electron microscopy revealed the average nanoparticle size to be 7.22±2.6 nm, while X-ray diffraction showed distinct 2θ peaks for iron and gold, confirming the presence of iron and gold nanoparticles. Inductively coupled plasma mass spectrometry revealed that the amount of NFA-MTX conjugate ingested by HepG2 cancer cells was 1.5 times higher than that ingested by L929 fibroblasts, thereby proving a higher selective ingestion by cancer cells compared to normal cells. Fourier-transform infrared spectroscopy revealed the breakage of Au-S bonds by the heat generated under magnetic field stimulation to release MTX from the NFA-MTX conjugate, triggering a 95% decrease in cellular viability at 100 µg/mL.

Conclusion: The ability of NFA-MTX to dissociate under the influence of an applied magnetic field provides a new strategy to induce cancer cell death via hyperthermia. Applications in drug delivery, drug development, and cancer research are expected.

Keywords: controlled drug release; hyperthermia; iron–gold nanoparticles; methotrexate; superparamagnetic.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Delayed-Action Preparations / pharmacology
  • Delayed-Action Preparations / therapeutic use*
  • Drug Liberation
  • Gold / chemistry*
  • Gold Alloys / chemistry*
  • Hep G2 Cells
  • Humans
  • Hyperthermia, Induced*
  • Iron / chemistry*
  • Magnetic Fields
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Methotrexate / chemistry
  • Methotrexate / therapeutic use
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Gold Alloys
  • Gold
  • Iron
  • Methotrexate