Synthesis and cytotoxicity analysis of fatty acid-mediated maghemite nanoparticles in cancerous and normal cells

Document Type : Research Paper

Authors

1 1. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Iran

2 1. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran 2.Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 1. Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2. Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 1. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

5 Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

6 1- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2-Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Our goal was to synthesize and characterize fatty acid-capped maghemite nanoparticles (NPs) and evaluate their cytotoxic effect on human cancer and normal cell lines.
Methods: Maghemite NPs were synthesized by co-precipitating iron (II) chloride tetrahydrate and iron (III) chloride hexahydrate, followed by surface capping with monounsaturated fatty acid, named oleic acid (OA). The particles were characterized using X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), vibrating-sample magnetometer (VSM), and Fourier-transform infrared spectroscopy (FTIR). The cytotoxicity of the capped NPs was assessed using an MTT assay.
Results: XRD analysis confirmed the formation of highly crystalline maghemite NPs with a cubic structure and an estimated crystallite size of approximately 9 nm. FE-SEM and TEM images revealed semi-spherical and cuboidal particles with an average size of 14 nm. EDS analysis confirmed the presence of iron, oxygen, carbon, and gold elements. VSM analysis demonstrated a saturation magnetization value of about 51 emu/g, while FTIR confirmed the successful capping of maghemite NPs with OA. The MTT assay showed that the NPs exhibited no cytotoxic effects on CaSki or HUVEC cells, even at the highest 50 µg/mL concentration.
Conclusion: The synthesized OA-capped maghemite NPs exhibited promising superparamagnetic properties with no significant cytotoxic effects on human cancer or normal cell lines, suggesting potential applications in biomedicine.

Keywords


  1. Ali A, Zafar H, Zia M, Haq I, Phull A, Ali J, et al. Synthesis, characterization, applications, and challenges of iron oxide nanoparticles. Nanotechnol Sci Appl. 2016;9:49-67.
  2. Ghamari Kargar P, Maleki B, Ghani M. Ag/GO/Fe3O4/γ-Fe2O3 Nanocomposite for Green-Light-Driven Photocatalytic Oxidation of 5-Hydroxymethylfurfural to 5-Hydroxymethyl-2-furancarboxylic Acid. ACS Appl Nano Mat. 2024;7(8):8765-8782.
  3. Tietze R, Zaloga J, Unterweger H, Lyer S, Friedrich RP, Janko C, et al. Magnetic nanoparticle-based drug delivery for cancer therapy. Biochem Biophys Res Commun. 2015;468(3):463-470.
  4. Chouhan R, Horvat M, Ahmed J, Alhokbany N, Alshehri S, Gandhi S. Magnetic Nanoparticles-A Multifunctional Potential Agent for Diagnosis and Therapy. Cancers (Basel). 2021;13(9).
  5. Bakht M, Sadeghi M, Pourbaghi-Masouleh M, Tenreiro C. Scope of Nanotechnology-based Radiation Therapy and Thermotherapy. Current Cancer Drug Targets. 2012;12(8):998-1015.
  6. Sun C, Lee JSH, Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Deliv Rev. 2008;60(11):1252-1265.
  7. Bae D, Han K, Cho S, Choi S. Synthesis of ultrafine Fe3O4 powder by glycothermal process. Mater Lett. 1998;37(4–5):255-258.
  8. Chen S, Feng J, Guo X, Hong J, Ding W. One-step wet chemistry for preparation of magnetite nanorods. Mater Lett. 2005;59(8-9):985-988.
  9. Yusefi M, Shameli K, Jumaat AF. Preparation and Properties of Magnetic Iron Oxide Nanoparticles for Biomedical Applications: A Brief Review. J Adv Res Mater Sci. 2020;75(1):10-18.
  10. Javed R, Zia M, Naz S, Aisida SO, Ain NU, Ao Q. Role of capping agents in the application of nanoparticles in biomedicine and environmental remediation: recent trends and future prospects. J Nanobiotechnology. 2020;18(1):172.
  11. Sales-Campos H, Souza PR, Peghini BC, da Silva JS, Cardoso CR. An Overview of the Modulatory Effects of Oleic Acid in Health and Disease. Mini Rev Med Chem. 2013;13(2):201-210.
  12. Yousefpoor Y, Baharifar H, Esnaashari S, Gheybi F, Mehrabi M, Osanloo M, et al. A review of topical micro- and nanoemulsions for common skin diseases. Nanomedicine J. 2024;11(3):205-221.
  13. Javed R, Zia M, Naz S, Aisida SO, Ain Nu, Ao Q. Role of capping agents in the application of nanoparticles in biomedicine and environmental remediation: recent trends and future prospects. J Nanobiotechnology. 2020;18(1):172.
  14. Díez AG, Rincón-Iglesias M, Lanceros-Méndez S, Reguera J, Lizundia E. Multicomponent magnetic nanoparticle engineering: the role of structure-property relationship in advanced applications. Mater Today Chem. 2022;26:101220.
  15. Szczyglewska P, Feliczak-Guzik A, Nowak I. Nanotechnology-General Aspects: A Chemical Reduction Approach to the Synthesis of Nanoparticles. Molecules. 2023;28(13):4932.
  16. Gholoobi A, Abnous K, Ramezani M, Homaei Shandiz F, Darroudi M, Ghayour-Mobarhan M, et al. Synthesis of γ-Fe2O3 Nanoparticles Capped with Oleic Acid and their Magnetic Characterization. Iran J Sci Technol A . 2017;42(4):1889-93.
  17. Rana P, Sharma S, Sharma R, Banerjee K. Apple pectin supported superparamagnetic (γ-Fe2O3) maghemite nanoparticles with antimicrobial potency. Mater Sci Energy Technol. 2019;2(1):15-21.
  18. Ansari MA, Asiri SMM. Green synthesis, antimicrobial, antibiofilm and antitumor activities of superparamagnetic gamma-Fe(2)O(3) NPs and their molecular docking study with cell wall mannoproteins and peptidoglycan. Int J Biol Macromol. 2021;171:44-58.
  19. Ghamari P, Maleki B, Ghani M. Fe3O4/Fe2O3/TiO2/Ag: an innovative photocatalyst under visible light irradiation in deep eutectic solvent for efficient conversion of 5-HMF to chemo-and bio-based chemicals besides their determination using HPLC. Biomass Convers Biorefin. 2023.
  20. Vidal-Vidal J, Rivas J, López-Quintela MA. Synthesis of monodisperse maghemite nanoparticles by the microemulsion method. Colloids Surf A: Physicochem Eng Asp. 2006;288(1-3):44-51.
  21. Nidhin M, Indumathy R, Sreeram K, Nair B. Synthesis of iron oxide nanoparticles of narrow size distribution on polysaccharide temolates. Bull Mater Sci. 2008;31:93-96
  22. Basavegowda N, Mishra K, Lee YR. Sonochemically synthesized ferromagnetic Fe3O4nanoparticles as a recyclable catalyst for the preparation of pyrrolo[3,4-c]quinoline-1,3-dione derivatives. RSC Adv. 2014;4(106):61660-6.
  23. Nyquist RA, Putzig CL, Kagel RO, Leugers MA. Handbook of Infrared and Raman Spectra of Inorganic Compounds and Organic Salts. Infrared Spectra of Inorganic Compounds: Elsevier Science; 1971.
  24. Zhang L, He R, Gu H-C. Oleic acid coating on the monodisperse magnetite nanoparticles. Appl Surf Sci. 2006;253(5):2611-7.
  25. Fereydouni N, Zangouei M, Darroudi M, Hosseinpour M, Gholoobi A. Antibacterial activity of chitosan-polyethylene oxide nanofibers containing silver nanoparticles against aerobic and anaerobic bacteria. J Mol Struct. 2023;1274:134304.
  26. Valdiglesias V, Kilic G, Costa C, Fernandez-Bertolez N, Pasaro E, Teixeira JP, et al. Effects of iron oxide nanoparticles: cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity. Environ Mol Mutagen. 2015;56(2):125-148.
  27. Repar N, Jovicic EJ, Kump A, Birarda G, Vaccari L, Erman A, et al. Oleic Acid Protects Endothelial Cells from Silica-Coated Superparamagnetic Iron Oxide Nanoparticles (SPIONs)-Induced Oxidative Stress and Cell Death. Int J Mol Sci. 2022;23(13).
  28. Matshaya TJ, Lanterna AE, Granados AM, Krause RW, Maggio B, Vico RV. Distinctive interactions of oleic acid covered magnetic nanoparticles with saturated and unsaturated phospholipids in Langmuir monolayers. Langmuir. 2014;30(20):5888-5896.
  29. Okassa LN, Marchais H, Douziech-Eyrolles L, Herve K, Cohen-Jonathan S, Munnier E, et al. Optimization of iron oxide nanoparticles encapsulation within poly(d,l-lactide-co-glycolide) sub-micron particles. Eur J Pharm Biopharm. 2007;67(1):31-38.
  30. Fernandez-Alvarez F, Caro C, Garcia-Garcia G, Garcia-Martin ML, Arias JL. Engineering of stealth (maghemite/PLGA)/chitosan (core/shell)/shell nanocomposites with potential applications for combined MRI and hyperthermia against cancer. J Mater Chem B. 2021;9(24):4963-4980.
  31. Saranya S, Vijayaranai K, Pavithra S, Raihana N, K. K. In vitro cytotoxicity of zinc oxide, iron oxide and copper nanopowders prepared by green synthesis. Toxicol Rep. 2017;4:427-430.
  32. Guardia P, Batlle-Brugal B, Roca AG, Iglesias O, Morales MP, Serna CJ, et al. Surfactant effects in magnetite nanoparticles of controlled size. J Magn Magn Mater. 2007;316(2):e756-e759.
  33. Coricovac DE, Moaca EA, Pinzaru I, Citu C, Soica C, Mihali CV, et al. Biocompatible Colloidal Suspensions Based on Magnetic Iron Oxide Nanoparticles: Synthesis, Characterization and Toxicological Profile. Front Pharmacol. 2017;8:154.
  34. Rahmani R, Gharanfoli M, Gholamin M, Darroudi M, Chamani J, Sadri K, et al. Plant-mediated synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) using aloe vera and flaxseed extracts and evaluation of their cellular toxicities. Ceram Int. 2020;46(3):3051-8.
  35. Bali Ogholbeyg A, Kianvash, A., Hajalilou, A. et al. Cytotoxicity characteristics of green assisted-synthesized superparamagnetic maghemite (γ-Fe2O3) nanoparticles. J Mater Sci Mater Electron. 2018;29, 12135(2143).
  36. Balas M, Predoi D, Burtea C, Dinischiotu A. New Insights into the Biological Response Triggered by Dextran-Coated Maghemite Nanoparticles in Pancreatic Cancer Cells and Their Potential for Theranostic Applications. Int J Mol Sci. 2023;24(4).
  37. Silva A, Carvalho N, Paterno L, Moura L, Filomeno C, Paula E, et al. Methylene blue associated with maghemite nanoparticles has antitumor activity in breast and ovarian carcinoma cell lines. Cancer Nanotechnol. 2021;12(1).
  38. Fernandez-Alvarez F, Garcia-Garcia G, Arias JL. A Tri-Stimuli Responsive (Maghemite/PLGA)/Chitosan Nanostructure with Promising Applications in Lung Cancer. Pharmaceutics. 2021;13(8).
  39. Sharifi M, Rezayat SM, Akhtari K, Hasan A, Falahati M. Fabrication and evaluation of anti-cancer efficacy of lactoferrin-coated maghemite and magnetite nanoparticles. J Biomol Struct Dyn. 2020;38(10):2945-2954.
  40. Ramos-Guivar JA, Morales MA, Litterst FJ. γ-Fe2O3 nanoparticles embedded in nanohydroxyapatite matrix for magnetic hyperthermia and in vitro osteoblast cell studies. Ceram Int. 2020;46(8):10658-10666.
  41. Predoi D AE, Balas M, Munteanu M, Dinischiotu A. Synthesis and characterization of bio-compatible maghemite nanoparticles. Dig J Nanomater Biostruct. 2010; 5(3):779-786.
  42. Khodabakhshi M, Bahari A. Investigation and Characterization of Maghemite (γ-Fe2O3) Nanoparticles and Its Cytotoxicity Studies. Indian J Pharm Educ Res. 2017;51(2):295-301.