Keratinocyte Biocompatibility of Biogenic Iron Nanoparticles — Oak Academic Publishing
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Keratinocyte Biocompatibility of Biogenic Iron Nanoparticles
Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue (CITAAC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Neuquén, Argentina
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Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba, Argentina
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Laboratorio de Bio-Nanotecnología, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina
,
Laboratorio de Bio-Nanotecnología, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina
,
Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba, Argentina
,
Centro de Investigación y Asistencia Técnica a la Industria (CIATI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Neuquén, Argentina
,
Instituto Multidisciplinario de Biología Vegetal (IMBIV), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina
,
Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue (CITAAC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Neuquén, Argentina
,
Departamento de Ciencias del Ambiente y la Salud, Facultad de Ciencias del Ambiente y la Salud, Universidad Nacional del Comahue, Neuquén, Argentina
,
Grupo de Biología Estructural y Biotecnología (GBEyB), IMBICE (CONICET CCT-La Plata), Buenos Aires, Argentina
,
Laboratorio de Nanosistemas de Aplicación Biotecnológica (LANSAB), Universidad Nacional de Hurlingham, Buenos Aires, Argentina
,
Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC), Buenos Aires, Argentina
,
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Haya de la Torre y Medina Allende, Córdoba, Argentina
,
Cátedra de Microbiología, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina
1 Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue (CITAAC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Neuquén, Argentina
2 Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba, Argentina
3 Laboratorio de Bio-Nanotecnología, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina
4 Laboratorio de Bio-Nanotecnología, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina
5 Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba, Argentina
6 Centro de Investigación y Asistencia Técnica a la Industria (CIATI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Neuquén, Argentina
7 Instituto Multidisciplinario de Biología Vegetal (IMBIV), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina
8 Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue (CITAAC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Neuquén, Argentina
9 Departamento de Ciencias del Ambiente y la Salud, Facultad de Ciencias del Ambiente y la Salud, Universidad Nacional del Comahue, Neuquén, Argentina
10 Grupo de Biología Estructural y Biotecnología (GBEyB), IMBICE (CONICET CCT-La Plata), Buenos Aires, Argentina
11 Laboratorio de Nanosistemas de Aplicación Biotecnológica (LANSAB), Universidad Nacional de Hurlingham, Buenos Aires, Argentina
12 Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC), Buenos Aires, Argentina
13 Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Haya de la Torre y Medina Allende, Córdoba, Argentina
14 Cátedra de Microbiología, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina
Iron nanoparticles (FeNPs) are promising candidates for medical purposes, including topical dermatological applications and skin absorption. This research investigated whether biologically synthesized FeNPs display potential toxic effects in human keratinocytes in vitro . Cell cultures were performed with the HaCaT keratinocyte cell line, which was exposed to FeNPs (0 - 214 µg/mL) for 4 and 24 h. Cell viability, reactive oxygen species production, cellular antioxidant components, and wound healing assays were analyzed. FeNPs did not alter the morphology of HaCaT cells, although low cellular cytotoxicity at the highest concentration was observed. The 214 µg/mL condition also altered cell migration as well as increased reactive oxygen species production. The obtained results have shown that biosynthetic FeNPs display low keratinocyte toxicity and could be explored as promising candidates to be used in local treatments as conjugates for drug delivery systems.
Choi, Y. and Lee, S.Y. (2020) Biosynthesis of Inorganic Nanomaterials Using Microbial Cells and Bacteriophages. Nature Reviews Chemistry , 4, 638-656. https://doi.org/10.1038/s41570-020-00221-w
Andleeb, A., Andleeb, A., Asghar, S., Zaman, G., Tariq, M., Mehmood, A., et al . (2021) A Systematic Review of Biosynthesized Metallic Nanoparticles as a Promising Anti-Cancer-Strategy. Cancers , 13, Article 2818. https://doi.org/10.3390/cancers13112818
Malhotra, N., Lee, J., Liman, R.A.D., Ruallo, J.M.S., Villaflores, O.B., Ger, T., et al . (2020) Potential Toxicity of Iron Oxide Magnetic Nanoparticles: A Review. Molecules , 25, Article 3159. https://doi.org/10.3390/molecules25143159
Cotin, G., Piant, S., Mertz, D., Felder-Flesch, D. and Begin-Colin, S. (2018) Iron Oxide Nanoparticles for Biomedical Applications: Synthesis, Functionalization, and Application. In: Mahmoudi, M. and Laurent, S., Eds., Iron Oxide Nanoparticles for Biomedical Applications , Elsevier, 43-88. https://doi.org/10.1016/b978-0-08-101925-2.00002-4
Ribeiro, A.I., Dias, A.M. and Zille, A. (2022) Synergistic Effects between Metal Nanoparticles and Commercial Antimicrobial Agents: A Review. ACS Applied Nano Materials , 5, 3030-3064. https://doi.org/10.1021/acsanm.1c03891
Park, T.J., Lee, K.G. and Lee, S.Y. (2015) Advances in Microbial Biosynthesis of Metal Nanoparticles. Applied Microbiology and Biotechnology , 100, 521-534. https://doi.org/10.1007/s00253-015-6904-7
Zafar, N., Madni, A., Khalid, A., Khan, T., Kousar, R., Naz, S.S., et al . (2020) Pharmaceutical and Biomedical Applications of Green Synthesized Metal and Metal Oxide Nanoparticles. Current Pharmaceutical Design , 26, 5844-5865. https://doi.org/10.2174/1381612826666201126144805
Franceschinis, G., Beverina, M., Corleto, M., Sosa, A.M., Lillo, C., Arias Casará, L., et al . (2023) Green-Synthesized Silver Nanoparticles Using Aloe Maculata Extract as Antibacterial Agent for Potential Topical Application. OpenNano , 12, Article ID: 100148. https://doi.org/10.1016/j.onano.2023.100148
Tsekhmistrenko, S.I., Bityutskyy, V.S., Tsekhmistrenko, O.S., Horalskyi, L.P., Tymoshok, N.O. and Spivak, M.Y. (2020) Bacterial Synthesis of Nanoparticles: A Green Approach. Biosystems Diversity , 28, 9-17. https://doi.org/10.15421/012002
Crespo, K.A., Baronetti, J.L., Quinteros, M.A., Páez, P.L. and Paraje, M.G. (2016) Intra-and Extracellular Biosynthesis and Characterization of Iron Nanoparticles from Prokaryotic Microorganisms with Anticoagulant Activity. Pharmaceutical Research , 34, 591-598. https://doi.org/10.1007/s11095-016-2084-0
Sundaram, P.A., Augustine, R. and Kannan, M. (2012) Extracellular Biosynthesis of Iron Oxide Nanoparticles by Bacillus subtilis Strains Isolated from Rhizosphere Soil. Biotechnology and Bioprocess Engineering , 17, 835-840. https://doi.org/10.1007/s12257-011-0582-9
Fatemi, M., Mollania, N., Momeni-Moghaddam, M. and Sadeghifar, F. (2018) Extracellular Biosynthesis of Magnetic Iron Oxide Nanoparticles by Bacillus Cereus Strain HMH1: Characterization and in Vitro Cytotoxicity Analysis on MCF-7 and 3T3 Cell Lines. Journal of Biotechnology , 270, 1-11. https://doi.org/10.1016/j.jbiotec.2018.01.021
Sani, A., Cao, C. and Cui, D. (2021) Toxicity of Gold Nanoparticles (AuNPs): A Review. Biochemistry and Biophysics Reports , 26, Article ID: 100991. https://doi.org/10.1016/j.bbrep.2021.100991
Abbasi, R., Shineh, G., Mobaraki, M., Doughty, S. and Tayebi, L. (2023) Structural Parameters of Nanoparticles Affecting Their Toxicity for Biomedical Applications: A Review. Journal of Nanoparticle Research , 25, Article No. 43. https://doi.org/10.1007/s11051-023-05690-w
Thomas, A., Sankaranarayanan, S.A. and Rengan, A.K. (2022) Modified Polyethylene Glycol Encapsulated Iron Oxide Nanoparticles for Accelerated Wound Healing Application. IEEE Transactions on Nanotechnology , 21, 1-5. https://doi.org/10.1109/tnano.2021.3138260
Rao, Y., Chen, W., Liang, X., Huang, Y., Miao, J., Liu, L., et al . (2014) Epirubicin-loaded Superparamagnetic Iron-Oxide Nanoparticles for Transdermal Delivery: Cancer Therapy by Circumventing the Skin Barrier. Small , 11, 239-247. https://doi.org/10.1002/smll.201400775
Murray, A.R., Kisin, E., Inman, A., Young, S., Muhammed, M., Burks, T., et al . (2012) Oxidative Stress and Dermal Toxicity of Iron Oxide Nanoparticles in Vitro . Cell Biochemistry and Biophysics , 67, 461-476. https://doi.org/10.1007/s12013-012-9367-9
Alili, L., Chapiro, S., Marten, G.U., Schmidt, A.M., Zanger, K. and Brenneisen, P. (2015) Effect of Fe 3 o 4 nanoparticles on Skin Tumor Cells and Dermal Fibroblasts. BioMed Research International , 2015, Article ID: 530957. https://doi.org/10.1155/2015/530957
Dowlath, M.J.H., Musthafa, S.A., Mohamed Khalith, S.B., Varjani, S., Karuppannan, S.K., Ramanujam, G.M., et al . (2021) Comparison of Characteristics and Biocompatibility of Green Synthesized Iron Oxide Nanoparticles with Chemical Synthesized Nanoparticles. Environmental Research , 201, Article ID: 111585. https://doi.org/10.1016/j.envres.2021.111585
Iqbal, J., Abbasi, B.A., Batool, R., Khalil, A.T., Hameed, S., Kanwal, S., et al . (2019) Biogenic Synthesis of Green and Cost Effective Cobalt Oxide Nanoparticles Using Geranium wallichianum Leaves Extract and Evaluation of in Vitro Antioxidant, Antimicrobial, Cytotoxic and Enzyme Inhibition Properties. Materials Research Express , 6, Article ID: 115407. https://doi.org/10.1088/2053-1591/ab4f04
Moacă, E., Watz, C.G., Flondor (Ionescu), D., Păcurariu, C., Tudoran, L.B., Ianoș, R., et al . (2022) Biosynthesis of Iron Oxide Nanoparticles: Physico-Chemical Characterization and Their in Vitro Cytotoxicity on Healthy and Tumorigenic Cell Lines. Nanomaterials , 12, Article 2012. https://doi.org/10.3390/nano12122012
Magogotya, M., Vetten, M., Roux-van der Merwe, M., Badenhorst, J. and Gulumian, M. (2022) In Vitro Toxicity and Internalization of Gold Nanoparticles (AuNPs) in Human Epithelial Colorectal Adenocarcinoma (Caco-2) Cells and the Human Skin Keratinocyte (HaCaT) Cells. Mutation Research / Genetic Toxicology and Environmental Mutagenesis , 883, 503556. https://doi.org/10.1016/j.mrgentox.2022.503556
Zanette, C., Pelin, M., Crosera, M., Adami, G., Bovenzi, M., Larese, F.F., et al . (2011) Silver Nanoparticles Exert a Long-Lasting Antiproliferative Effect on Human Keratinocyte HaCaT Cell Line. Toxicology in Vitro , 25, 1053-1060. https://doi.org/10.1016/j.tiv.2011.04.005
Perveen, S., Nadeem, R., Rehman, S.u., Afzal, N., Anjum, S., Noreen, S., et al . (2022) Green Synthesis of Iron (Fe) Nanoparticles Using Plumeria obtusa Extract as a Reducing and Stabilizing Agent: Antimicrobial, Antioxidant and Biocompatibility Studies. Arabian Journal of Chemistry , 15, Article ID: 103764. https://doi.org/10.1016/j.arabjc.2022.103764
Zangeneh, A., Zangeneh, M.M. and Moradi, R. (2019) Ethnomedicinal Plant-Extract‐assisted Green Synthesis of Iron Nanoparticles Using Allium saralicum Extract, and Their Antioxidant, Cytotoxicity, Antibacterial, Antifungal and Cutaneous Wound‐healing Activities. Applied Organometallic Chemistry , 34, e5247. https://doi.org/10.1002/aoc.5247
Bustos, P.S., Quinteros, M.d.l.Á., Gomez, D.S., Ortega, M.G., Páez, P.L. and Guiñazú, N.L. (2021) Silver Bionanoparticles Toxicity in Trophoblast Is Mediated by Nitric Oxide and Glutathione Pathways. Toxicology , 454, Article ID: 152741. https://doi.org/10.1016/j.tox.2021.152741
Zhang, J., Wang, W. and Mao, X. (2020) Chitopentaose Protects HaCaT Cells against H 2 O 2 -Induced Oxidative Damage through Modulating MAPKs and Nrf2/ARE Signaling Pathways. Journal of Functional Foods , 72, Article ID: 104086. https://doi.org/10.1016/j.jff.2020.104086
Calienni, M.N., Temprana, C.F., Prieto, M.J., Paolino, D., Fresta, M., Tekinay, A.B., et al . (2017) Nano-Formulation for Topical Treatment of Precancerous Lesions: Skin Penetration, in Vitro , and in Vivo Toxicological Evaluation. Drug Delivery and Translational Research , 8, 496-514. https://doi.org/10.1007/s13346-017-0469-1
Grada, A., Otero-Vinas, M., Prieto-Castrillo, F., Obagi, Z. and Falanga, V. (2017) Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay. Journal of Investigative Dermatology , 137, e11-e16. https://doi.org/10.1016/j.jid.2016.11.020
Kumar, P., Nagarajan, A. and Uchil, P.D. (2018) Analysis of Cell Viability by the MTT Assay. Cold Spring Harbor Protocols , No. 6, 469-471. https://doi.org/10.1101/pdb.prot095505
Feoktistova, M., Geserick, P. and Leverkus, M. (2016) Crystal Violet Assay for Determining Viability of Cultured Cells. Cold Spring Harbor Protocols , No. 4, 343-346. https://doi.org/10.1101/pdb.prot087379
Repetto, G., del Peso, A. and Zurita, J.L. (2008) Neutral Red Uptake Assay for the Estimation of Cell Viability/cytotoxicity. Nature Protocols , 3, 1125-1131. https://doi.org/10.1038/nprot.2008.75
Narayanan, K.B. and Sakthivel, N. (2010) Biological Synthesis of Metal Nanoparticles by Microbes. Advances in Colloid and Interface Science , 156, 1-13. https://doi.org/10.1016/j.cis.2010.02.001
Kianpour, S., Ebrahiminezhad, A., Negahdaripour, M., Mohkam, M., Mohammadi, F., Niknezhad, S.V., et al . (2018) Characterization of Biogenic Fe (III)-Binding Exopolysaccharide Nanoparticles Produced by Ralstonia sp. Sk 03. Biotechnology Progress , 34, 1167-1176. https://doi.org/10.1002/btpr.2660
Jubran, A.S., Al-Zamely, O.M. and Al-Ammar, M.H. (2020) A Study of Iron Oxide Nanoparticles Synthesis by Using Bacteria. International Journal of Pharmaceutical Quality Assurance , 11, 88-92. https://doi.org/10.25258/ijpqa.11.1.13
Jiang, X., Fan, X., Xu, W., Zhang, R. and Wu, G. (2019) Biosynthesis of Bimetallic Au-Ag Nanoparticles Using Escherichia coli and Its Biomedical Applications. ACS Biomaterials Science & Engineering , 6, 680-689. https://doi.org/10.1021/acsbiomaterials.9b01297
Mi, C., Wang, Y., Zhang, J., Huang, H., Xu, L., Wang, S., et al . (2011) Biosynthesis and Characterization of CDs Quantum Dots in Genetically Engineered Escherichia coli . Journal of Biotechnology , 153, 125-132. https://doi.org/10.1016/j.jbiotec.2011.03.014
Gurunathan, S., Kalishwaralal, K., Vaidyanathan, R., Venkataraman, D., Pandian, S.R.K., Muniyandi, J., et al . (2009) Biosynthesis, Purification and Characterization of Silver Nanoparticles Using Escherichia coli . Colloids and Surfaces B : Biointerfaces , 74, 328-335. https://doi.org/10.1016/j.colsurfb.2009.07.048
Murillo-Rábago, E.I., Vilchis-Nestor, A.R., Juarez-Moreno, K., Garcia-Marin, L.E., Quester, K. and Castro-Longoria, E. (2022) Optimized Synthesis of Small and Stable Silver Nanoparticles Using Intracellular and Extracellular Components of Fungi: An Alternative for Bacterial Inhibition. Antibiotics , 11, Article 800. https://doi.org/10.3390/antibiotics11060800
Nkosi, N.C., Basson, A.K., Ntombela, Z.G., Dlamini, N.G. and Pullabhotla, R.V.S.R. (2025) Green Synthesis and Characterization of Iron Nanoparticles Synthesized from Bioflocculant for Wastewater Treatment: A Review. Biotechnology Notes , 6, 10-31. https://doi.org/10.1016/j.biotno.2024.12.001
Siglienti, I., Bendszus, M., Kleinschnitz, C. and Stoll, G. (2006) Cytokine Profile of Iron-Laden Macrophages: Implications for Cellular Magnetic Resonance Imaging. Journal of Neuroimmunology , 173, 166-173. https://doi.org/10.1016/j.jneuroim.2005.11.011
Moore, A., Marecos, E., Bogdanov, A. and Weissleder, R. (2000) Tumoral Distribution of Long-Circulating Dextran-Coated Iron Oxide Nanoparticles in a Rodent Model. Radiology , 214, 568-574. https://doi.org/10.1148/radiology.214.2.r00fe19568
Berry, C.C., Wells, S., Charles, S., Aitchison, G. and Curtis, A.S.G. (2004) Cell Response to Dextran-Derivatised Iron Oxide Nanoparticles Post Internalisation. Biomaterials , 25, 5405-5413. https://doi.org/10.1016/j.biomaterials.2003.12.046
Sathiyaseelan, A., Saravanakumar, K., Mariadoss, A.V.A. and Wang, M. (2021) Antimicrobial and Wound Healing Properties of FeO Fabricated Chitosan/PVA Nanocomposite Sponge. Antibiotics , 10, Article 524. https://doi.org/10.3390/antibiotics10050524
Zangeneh, M.M., Ghaneialvar, H., Akbaribazm, M., Ghanimatdan, M., Abbasi, N., Goorani, S., et al . (2019) Novel Synthesis of Falcaria vulgaris Leaf Extract Conjugated Copper Nanoparticles with Potent Cytotoxicity, Antioxidant, Antifungal, Antibacterial, and Cutaneous Wound Healing Activities under in Vitro and in Vivo Condition. Journal of Photochemistry and Photobiology B : Biology , 197, Article ID: 111556. https://doi.org/10.1016/j.jphotobiol.2019.111556
Nahari, M.H., Al Ali, A., Asiri, A., Mahnashi, M.H., Shaikh, I.A., Shettar, A.K., et al . (2022) Green Synthesis and Characterization of Iron Nanoparticles Synthesized from Aqueous Leaf Extract of Vitex Leucoxylon and Its Biomedical Applications. Nanomaterials , 12, Article 2404. https://doi.org/10.3390/nano12142404
Coricovac, D., Moacă, E., Pinzaru, I., Cîtu, C., Soica, C., Mihali, C., et al . (2017) Biocompatible Colloidal Suspensions Based on Magnetic Iron Oxide Nanoparticles: Synthesis, Characterization and Toxicological Profile. Frontiers in Pharmacology , 8, Article 154. https://doi.org/10.3389/fphar.2017.00154
Nowak-Jary, J. and Machnicka, B. (2024) Comprehensive Analysis of the Potential Toxicity of Magnetic Iron Oxide Nanoparticles for Medical Applications: Cellular Mechanisms and Systemic Effects. International Journal of Molecular Sciences , 25, Article 12013. https://doi.org/10.3390/ijms252212013
Amin, R.M., Abdelmonem, A., Verwanger, T., Elsherbini, E. and Krammer, B. (2014) Cytotoxicity of Magnetic Nanoparticles on Normal and Malignant Human Skin Cells. Nano LIFE , 4, Article ID: 1440002. https://doi.org/10.1142/s1793984414400029
Arias, L.S., Pessan, J.P., Vieira, A.P.M., Lima, T.M.T.d., Delbem, A.C.B. and Monteiro, D.R. (2018) Iron Oxide Nanoparticles for Biomedical Applications: A Perspective on Synthesis, Drugs, Antimicrobial Activity, and Toxicity. Antibiotics , 7, Article 46. https://doi.org/10.3390/antibiotics7020046
Abakumov, M.A., Semkina, A.S., Skorikov, A.S., Vishnevskiy, D.A., Ivanova, A.V., Mironova, E., et al . (2018) Toxicity of Iron Oxide Nanoparticles: Size and Coating Effects. Journal of Biochemical and Molecular Toxicology , 32, e22225. https://doi.org/10.1002/jbt.22225
Snezhkina, A.V., Kudryavtseva, A.V., Kardymon, O.L., Savvateeva, M.V., Melnikova, N.V., Krasnov, G.S., et al . (2019) ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells. Oxidative Medicine and Cellular Longevity , 2019, Article ID: 6175804. https://doi.org/10.1155/2019/6175804
Yarjanli, Z., Ghaedi, K., Esmaeili, A., Rahgozar, S. and Zarrabi, A. (2017) Iron Oxide Nanoparticles May Damage to the Neural Tissue through Iron Accumulation, Oxidative Stress, and Protein Aggregation. BMC Neuroscience , 18, Article No. 51. https://doi.org/10.1186/s12868-017-0369-9