Toxicity evaluation of monodisperse PEGylated magnetic nanoparticles for nanomedicine

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

Acknowledgements

We thank Helena Nagyova and Edita Mrvikova for technical help.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work is supported by Grantová Agentura České Republiky; Ministry of Education, Youth and Sport of the Czech Republic. This work is also supported by the Czech Science Foundation (No. 17-04918S), MEYS (LQ1604 NPU II), and ERDF and MEYS (CZ.1.05/1.1.00/02.0109 BIOCEV) is acknowledged. Biological experiments were supported by the QualityNano project INFRA-2010-1.1.31 (No. 214547-2), NFM (No. SK0020), ERA-NET Euronanomed II Innocent and GEMNS, ITMS of the Operational research and development program from the ERDF (No. 26240120033), Brno University of Technology (FCH-S-15-2827), and the International Research and Innovation in Medicine Program at Cedars-Sinai Medical Center and the RECOOP Association.