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Effects of folate-conjugated Fe2O3@Au core–shell nanoparticles on oxidative stress markers, DNA damage, and histopathological characteristics: evidence from in vitro and in vivo studies

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Abstract

The aim of this work was to assess the cytotoxicity, genotoxicity, and histopathological effects of Fe2O3@Au-FA NPs using in vitro and in vivo models. Cytotoxicity and cellular uptake of nanoparticles (NPs) by HUVECs were examined via 3‐(4, 5‐Dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT) assay and inductively coupled plasma-mass-spectrometry (ICP-MS). This safe dose was then used for cytotoxicity assays, including total protein, total antioxidant capacity, lipid peroxidation, cell membrane integrity, reactive oxygen species, enzyme activity, and DNA damage. In the animal model, 32 Wistar rats were randomly categorized into 4 groups and received intraperitoneal injections of NPs. Blood samples for biochemical properties and histopathological changes were investigated. MTT results indicated 20 μg/ml as the safe dose for NPs. According to ICP-MS, treated cells showed significantly higher levels of the intracellular content of Fe (p < 0.001) and Au (p < 0.01) compared with the control group. In vitro tests did not show any significant cytotoxicity or genotoxicity at the safe dose of NPs. We found no significant elevation in intracellular γ-H2AX levels after treatment of HUVEC cells with Fe2O3@Au core–shell NPs (P > 0.05). As for the in vivo analysis, we observed no marked difference in serum biochemical parameters of rats treated with 50 mg/kg and 100 mg/kg doses of our NPs. Histopathological assessments indicated that liver, kidney, and testis tissues were not significantly affected at 50 mg/kg (liver), 50 mg/kg, and 100 mg/kg (kidney and testis) on NPs administration. These findings imply that the nanotoxicity of Fe2O3@Au-FA NPs in HUVECs and animals depends largely on the administrated dose. Our study suggests that Fe2O3@Au-FA NPs at a safe dose could be considered as new candidates in nanobiomedicine.

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Acknowledgements

This study was conducted under supervision and financial support of Zahedan University of Medical Sciences

Funding

This study was conducted under supervision and financial support of Zahedan University of Medical Sciences (IR.ZAUMS.REC.1399.135).

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Authors and Affiliations

  1. Pharmacology Research Center, Zahedan University of Medical Sciences, Postal Code: 9816743463, Zahedan, Iran

    Habib Ghaznavi, Omolbanin Shahraki & Roghayeh Sheervalilou

  2. Basic Veterinary Science Department, Veterinary medicine Faculty, University of Zabol, Postal Code: 9861335856, Zabol, Iran

    Mohammad Reza Hajinezhad

  3. Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Postal Code: 5166614766, Tabriz, Iran

    Milad Shirvaliloo

  4. Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Postal Code: 9816743463, Zahedan, Iran

    Sheida Shahraki, Ramin Saravani, Roghayeh Sheervalilou & Saman Sargazi

  5. Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran

    Kourosh Shahraki

  6. Finetech in Medicine Research Center, Iran University of Medical Sciences, Postal Code: 1449614535, Tehran, Iran

    Sakine Shirvalilou

  7. Material Engineering Department, College of Science Koç University, Istanbul, 34450, 1449614535, Turkey

    Ziba Nazarlou

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  1. Habib Ghaznavi
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Contributions

All authors contributed in different parts of the original study. MS, RS, MRH and SS wrote the main manuscript text. RS, MRH, SS, SS, OS, and SS conducted the different tests. KS, RS, ZN, MS, and RS edited the final draft.

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Correspondence to Roghayeh Sheervalilou or Saman Sargazi.

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Ghaznavi, H., Hajinezhad, M.R., Shirvaliloo, M. et al. Effects of folate-conjugated Fe2O3@Au core–shell nanoparticles on oxidative stress markers, DNA damage, and histopathological characteristics: evidence from in vitro and in vivo studies. Med Oncol 39, 122 (2022). https://doi.org/10.1007/s12032-022-01713-z

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