Toxicity evaluation of monodisperse PEGylated magnetic nanoparticles for nanomedicine

Nanotoxicology. 2019 May;13(4):510-526. doi: 10.1080/17435390.2018.1555624. Epub 2019 Feb 1.

Abstract

Innovative nanotechnology aims to develop particles that are small, monodisperse, smart, and do not cause unintentional side effects. Uniform magnetic Fe3O4 nanoparticles (12 nm in size) were prepared by thermal decomposition of iron(III) oleate. To make them colloidally stable and dispersible in water and cell culture medium, they were modified with phosphonic acid- (PA) and hydroxamic acid (HA)-terminated poly(ethylene glycol) yielding PA-PEG@Fe3O4 and HA-PEG@Fe3O4 nanoparticles; conventional γ-Fe2O3 particles were prepared as a control. Advanced techniques were used to evaluate the properties and safety of the particles. Completeness of the nanoparticle coating was tested by real-time polymerase chain reaction. Interaction of the particles with primary human peripheral blood cells, cellular uptake, cytotoxicity, and immunotoxicity were also investigated. Amount of internalized iron in peripheral blood mononuclear cells was 72, 38, and 25 pg Fe/cell for HA-PEG@Fe3O4, γ-Fe2O3, and PA-PEG@Fe3O4, respectively. Nanoparticles were localized within the cytoplasm and in the extracellular space. No cytotoxic effect of both PEGylated nanoparticles was observed (0.12-75 μg/cm2) after 24 and 72-h incubation. Moreover, no suppressive effect was found on the proliferative activity of T-lymphocytes and T-dependent B-cell response, phagocytic activity of monocytes and granulocytes, and respiratory burst of phagocytes. Similarly, no cytotoxic effect of γ-Fe2O3 particles was observed. However, they suppressed the proliferative activity of T-lymphocytes (75 μg/cm2, 72 h) and also decreased the phagocytic activity of monocytes (15 μg/cm2, 24 h; 3-75 μg/cm2, 72 h). We thus show that newly developed particles have great potential especially in cancer diagnostics and therapy.

Keywords: Iron oxide nanoparticles; PCR inhibition; cell interaction and uptake; cytotoxicity and immunotoxicity; human peripheral blood leucocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Cells, Cultured
  • Cytokines / metabolism
  • Humans
  • Hydroxamic Acids / chemistry
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / pathology
  • Magnetite Nanoparticles / chemistry
  • Magnetite Nanoparticles / toxicity*
  • Nanomedicine / methods*
  • Particle Size
  • Phagocytosis / drug effects
  • Phagocytosis / immunology
  • Phosphorous Acids / chemistry
  • Polyethylene Glycols / chemistry
  • Respiratory Burst / drug effects
  • Respiratory Burst / immunology
  • Surface Properties

Substances

  • Cytokines
  • Hydroxamic Acids
  • Magnetite Nanoparticles
  • Phosphorous Acids
  • phosphonic acid
  • Polyethylene Glycols