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Superparamagnetic iron oxide nanoparticles exacerbate the risks of reactive oxygen species-mediated external stresses

  • Inorganic Compounds
  • Published:
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Abstract

Superparamagnetic iron oxide nanoparticles (IONPs) have been widely applied in numerous biomedical fields. The evaluation of the toxicity of IONPs to the environment and human beings is indispensable to guide their applications. IONPs are usually considered to have good biocompatibility; however, some literatures have reported the toxicity of IONPs in vitro and in vivo. The controversy surrounding the biocompatibility of IONPs prompted us to carefully consider the biological effects of IONPs, especially under stress conditions. However, the potential risks of IONPs under stress conditions have not yet been evaluated in depth. Acrolein is widespread in the environment and modulates stress-induced gene activation and cell death in many organs and tissues. In this study, we assessed the sensitivity of H9c2 cardiomyocyte cells embedded with IONPs to acrolein and investigated the possible molecular mechanisms involved in this sensitivity. IONPs, which alone exhibited no toxicity, sensitized the H9c2 cardiomyocytes to acrolein-induced dysfunction. The IONP/acrolein treatment induced a loss of viability, membrane disruption, reactive oxygen species (ROS) generation, Erk activation, mitochondrial and lysosomal dysfunction, and necrosis in H9c2 cells. Treatment with an ROS generation inhibitor (diphenyleneiodonium) or an iron chelator (deferoxamine) prevented the IONP/acrolein-induced loss of viability, suggesting that ROS and IONP degradation facilitated the toxicity of the IONP/acrolein treatment in H9c2 cells. Our data suggest that cells embedded in IONPs are more vulnerable to oxidative stress, which confirms the hypothesis that nanoparticles can sensitize cells to the adverse effects of external stimulation. The present work provides a new perspective from which to evaluate the interactions between nanoparticles and cells.

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Abbreviations

AO:

Acridine orange

ATP:

Adenosine 5′-triphosphate

BCA:

Bicinchoninic acid assay

BSA:

Bovine serum albumin

DHE:

Dihydroethidium

DLS:

Dynamic light scattering

DMEM:

Dulbecco’s modified eagle medium

DNPH:

2,4-Dinitrophenylhydrazine

DPI:

Diphenyleneiodonium

EGF:

Epidermal growth factor

Erk:

Extracellular signal-regulated kinase

ESCs:

Embryonic stem cells

FBS:

Fetal bovine serum

GSH:

Glutathione reduced

HCM:

Human cardiac myocytes

IONPs:

Superparamagnetic iron oxide nanoparticles

JC-1:

CBIC2(3), 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetra ethylbenzimidazolylcarbocyanine iodide

JNK:

c-Jun N-terminal kinase

LAMP1:

Lysosome-associated membrane protein 1

LDH:

Lactate dehydrogenase

MDC:

Monodansylcadaverine

MTT:

3-(4,5)-Dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide

MRI:

Magnetic resonance imaging

NDA:

2,3-Naphthalenedicarboxaldehyde

NOX:

Nicotinamide adenine dinucleotide phosphate oxidase

PBS:

Phosphate-buffered saline

PI:

Propidium iodide

RIP:

Receptor-interacting protein

ROS:

Reactive oxygen species

tBHP:

Tert-butyl hydroperoxide

TEM:

Transmission electron microscope

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Acknowledgments

This study was partially supported by the National Natural Science Foundation of China, Key Program 30930105, Foundation of Xi’an Jiaotong University, New Century Excellent Talents in University, the National Natural Science Foundation of China (Grant No. 31070740), and the 985 and 211 Projects of Xi’an Jiaotong University.

Conflict of interest

The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

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Authors and Affiliations

  1. The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Frontier Institute of Science and Technology, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, China

    Cheng Luo, Liang Yang, Xun Wang, Jiangang Long & Jiankang Liu

  2. The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Bioinformatics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, China

    Yan Li

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  1. Cheng Luo
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Correspondence to Jiankang Liu.

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Luo, C., Li, Y., Yang, L. et al. Superparamagnetic iron oxide nanoparticles exacerbate the risks of reactive oxygen species-mediated external stresses. Arch Toxicol 89, 357–369 (2015). https://doi.org/10.1007/s00204-014-1267-x

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