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Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo

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Summary

Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines. Superparamagnetic iron oxide nanoparticles (SPION) are effective carriers for targeted drug delivery. This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI) (SPION-PEI) designed for small interfering RNA (siRNA) delivery both in vitro and in vivo. SPION-PEI/siRNA complexes were prepared at different weight ratios. Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). Rats were divided into three groups: a control group, a normal-saline group and a SPION-PEI/siRNA group. After a single intravenous injection, in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart, liver, spleen, lung and kidney 8 h, 24 h, and 7 days after the injection. Their distribution was histologically studied at the three time points by measuring ironpositive areas (μm2) in organ sections stained with Prussian blue. The same organs were analyzed by H&E staining for any possible histopathological changes. Furthermore, biochemical indexes such as alanine amino transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN) and creatinine (CREA) were also assessed at all experimental time points. Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4. MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity. In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition. The iron content was significantly increased in the liver and spleen, peaking 24 h after intravenous injection and then declining gradually. No evidence was found of irreversible histopathological damage to any of the organs tested. These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen, which might be the target organs of SPION-PEI/siRNA complexes. SPIONPEI/siRNA may serve as in vivo carrier for biomedical medicines.

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Authors and Affiliations

  1. Department of Clinical Laboratory, Wuhan Blood Center, Wuhan, 430000, China

    Qin Yu, Lei Zhao, Ting-ting Xu, Hao Bi & Rong Fu

  2. School of Chemistry and Life Science, Hubei University of Education, Wuhan, 430205, China

    Xiao-qin Xiong

  3. Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China

    Qian-hua Wang

Authors
  1. Qin Yu
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  2. Xiao-qin Xiong
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  3. Lei Zhao
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  4. Ting-ting Xu
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  5. Hao Bi
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  6. Rong Fu
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  7. Qian-hua Wang
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Correspondence to Qian-hua Wang.

Additional information

This work was supported by the National Natural Science Foundation of China (Nos. 81402640, 81502816), the Natural Science Foundation of Hubei Province (No. 2014CFB406), the Health and Family Planning Commission of Wuhan City (No. WX15B23) and Training Plan for Young and Middleaged Backbone Talents in Wuhan [No. 2014 (77)].

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Yu, Q., Xiong, Xq., Zhao, L. et al. Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo. CURR MED SCI 38, 1096–1102 (2018). https://doi.org/10.1007/s11596-018-1989-8

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  • DOI: https://doi.org/10.1007/s11596-018-1989-8

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