Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles

In the context of improving radiation therapy, high-atomic number (Z) metallic nanoparticles and, more importantly, gold-based nanostructures are developed as radiation enhancers/radiosensitizers. Due to the diversity of cell lines, nanoparticles, as well as radiation types or doses, the resulting b...

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Main Authors: Ioanna Tremi, Sophia Havaki, Sofia Georgitsopoulou, Georgia Terzoudi, Ioannis N. Lykakis, George Iliakis, Vasilios Georgakilas, Vassilis G. Gorgoulis, Alexandros G. Georgakilas
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/20/5086
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author Ioanna Tremi
Sophia Havaki
Sofia Georgitsopoulou
Georgia Terzoudi
Ioannis N. Lykakis
George Iliakis
Vasilios Georgakilas
Vassilis G. Gorgoulis
Alexandros G. Georgakilas
author_facet Ioanna Tremi
Sophia Havaki
Sofia Georgitsopoulou
Georgia Terzoudi
Ioannis N. Lykakis
George Iliakis
Vasilios Georgakilas
Vassilis G. Gorgoulis
Alexandros G. Georgakilas
author_sort Ioanna Tremi
collection DOAJ
description In the context of improving radiation therapy, high-atomic number (Z) metallic nanoparticles and, more importantly, gold-based nanostructures are developed as radiation enhancers/radiosensitizers. Due to the diversity of cell lines, nanoparticles, as well as radiation types or doses, the resulting biological effects may differ and remain obscure. In this multiparameter study, we aim to shed light on these effects and investigate them further by employing X-irradiation and three human cancer cell lines (PC3, A549, and U2OS cells) treated by multiple techniques. TEM experiments on PC3 cells showed that citrate-capped AuNPs were found to be located mostly in membranous structures/vesicles or autophagosomes, but also, in the case of PEG-capped AuNPs, inside the nucleus as well. The colony-forming capability of cancer cells radiosensitized by AuNPs decreased significantly and the DNA damage detected by cytogenetics, γH2AX immunostaining, and by single (γH2AX) or double (γH2AX and OGG1) immunolocalization via transmission electron microscopy (TEM) was in many cases higher and/or persistent after combination with AuNPs than upon individual exposure to ionizing radiation (IR). Moreover, different cell cycle distribution was evident in PC3 but not A549 cells after treatment with AuNPs and/or irradiation. Finally, cellular senescence was investigated by using a newly established staining procedure for lipofuscin, based on a Sudan Black-B analogue (GL13) which showed that based on the AuNPs’ concentration, an increased number of senescent cells might be observed after exposure to IR. Even though different cell lines or different types and concentrations of AuNPs may alter the levels of radiosensitization, our results imply that the complexity of damage might also be an important factor of AuNP-induced radiosensitization.
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spelling doaj.art-5e32ab0a5e2249b6a7c230838bb643372023-11-23T23:21:44ZengMDPI AGCancers2072-66942022-10-011420508610.3390/cancers14205086Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold NanoparticlesIoanna Tremi0Sophia Havaki1Sofia Georgitsopoulou2Georgia Terzoudi3Ioannis N. Lykakis4George Iliakis5Vasilios Georgakilas6Vassilis G. Gorgoulis7Alexandros G. Georgakilas8DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, Zografou Campus, National Technical University of Athens (NTUA), 15780 Athens, GreeceMolecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, GreeceDepartment of Material Science, University of Patras, 26504 Patras, GreeceLaboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety (INRASTES), National Centre for Scientific Research “Demokritos”, 15310 Athens, GreeceDepartment of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, GreeceDivision of Experimental Radiation Biology, Department of Radiation Therapy, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyDepartment of Material Science, University of Patras, 26504 Patras, GreeceMolecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, GreeceDNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, Zografou Campus, National Technical University of Athens (NTUA), 15780 Athens, GreeceIn the context of improving radiation therapy, high-atomic number (Z) metallic nanoparticles and, more importantly, gold-based nanostructures are developed as radiation enhancers/radiosensitizers. Due to the diversity of cell lines, nanoparticles, as well as radiation types or doses, the resulting biological effects may differ and remain obscure. In this multiparameter study, we aim to shed light on these effects and investigate them further by employing X-irradiation and three human cancer cell lines (PC3, A549, and U2OS cells) treated by multiple techniques. TEM experiments on PC3 cells showed that citrate-capped AuNPs were found to be located mostly in membranous structures/vesicles or autophagosomes, but also, in the case of PEG-capped AuNPs, inside the nucleus as well. The colony-forming capability of cancer cells radiosensitized by AuNPs decreased significantly and the DNA damage detected by cytogenetics, γH2AX immunostaining, and by single (γH2AX) or double (γH2AX and OGG1) immunolocalization via transmission electron microscopy (TEM) was in many cases higher and/or persistent after combination with AuNPs than upon individual exposure to ionizing radiation (IR). Moreover, different cell cycle distribution was evident in PC3 but not A549 cells after treatment with AuNPs and/or irradiation. Finally, cellular senescence was investigated by using a newly established staining procedure for lipofuscin, based on a Sudan Black-B analogue (GL13) which showed that based on the AuNPs’ concentration, an increased number of senescent cells might be observed after exposure to IR. Even though different cell lines or different types and concentrations of AuNPs may alter the levels of radiosensitization, our results imply that the complexity of damage might also be an important factor of AuNP-induced radiosensitization.https://www.mdpi.com/2072-6694/14/20/5086gold nanoparticles (AuNPs)ionizing radiation (IR)radiosensitizationclonogenic assayDNA damageγH2AX
spellingShingle Ioanna Tremi
Sophia Havaki
Sofia Georgitsopoulou
Georgia Terzoudi
Ioannis N. Lykakis
George Iliakis
Vasilios Georgakilas
Vassilis G. Gorgoulis
Alexandros G. Georgakilas
Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles
Cancers
gold nanoparticles (AuNPs)
ionizing radiation (IR)
radiosensitization
clonogenic assay
DNA damage
γH2AX
title Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles
title_full Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles
title_fullStr Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles
title_full_unstemmed Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles
title_short Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles
title_sort biological response of human cancer cells to ionizing radiation in combination with gold nanoparticles
topic gold nanoparticles (AuNPs)
ionizing radiation (IR)
radiosensitization
clonogenic assay
DNA damage
γH2AX
url https://www.mdpi.com/2072-6694/14/20/5086
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