{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:53:17Z","timestamp":1790034797353,"version":"4.0.1"},"reference-count":116,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001655","name":"DAAD \u201cHochschulpartnerschaften mit Griechenland\u201d","doi-asserted-by":"publisher","award":["57513880"],"award-info":[{"award-number":["57513880"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001655","name":"DAAD \u201cHochschulpartnerschaften mit Griechenland\u201d","doi-asserted-by":"publisher","award":["MIS-5000432"],"award-info":[{"award-number":["MIS-5000432"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003447","name":"Greece and the European Union","doi-asserted-by":"publisher","award":["57513880"],"award-info":[{"award-number":["57513880"]}],"id":[{"id":"10.13039\/501100003447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003447","name":"Greece and the European Union","doi-asserted-by":"publisher","award":["MIS-5000432"],"award-info":[{"award-number":["MIS-5000432"]}],"id":[{"id":"10.13039\/501100003447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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, \u03b3H2AX immunostaining, and by single (\u03b3H2AX) or double (\u03b3H2AX 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\u2019 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.<\/jats:p>","DOI":"10.3390\/cancers14205086","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T21:11:51Z","timestamp":1666041111000},"page":"5086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4711-8888","authenticated-orcid":false,"given":"Ioanna","family":"Tremi","sequence":"first","affiliation":[{"name":"DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, Zografou Campus, National Technical University of Athens (NTUA), 15780 Athens, Greece"},{"name":"Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Havaki","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8086-3508","authenticated-orcid":false,"given":"Sofia","family":"Georgitsopoulou","sequence":"additional","affiliation":[{"name":"Department of Material Science, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6213-5072","authenticated-orcid":false,"given":"Georgia","family":"Terzoudi","sequence":"additional","affiliation":[{"name":"Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety (INRASTES), National Centre for Scientific Research \u201cDemokritos\u201d, 15310 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8165-5604","authenticated-orcid":false,"given":"Ioannis N.","family":"Lykakis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-5342","authenticated-orcid":false,"given":"George","family":"Iliakis","sequence":"additional","affiliation":[{"name":"Division of Experimental Radiation Biology, Department of Radiation Therapy, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"},{"name":"Institute of Medical Radiation Biology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6674-1272","authenticated-orcid":false,"given":"Vasilios","family":"Georgakilas","sequence":"additional","affiliation":[{"name":"Department of Material Science, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9001-4112","authenticated-orcid":false,"given":"Vassilis G.","family":"Gorgoulis","sequence":"additional","affiliation":[{"name":"Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece"},{"name":"Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, 11527 Athens, Greece"},{"name":"Faculty Institute for Cancer Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester MP13 9PL, UK"},{"name":"Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece"},{"name":"Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5971-0010","authenticated-orcid":false,"given":"Alexandros 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ImmunoTher. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/S1470-2045(17)30457-6","article-title":"First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): A combined analysis of three multicentre, randomised, phase 3 trials","volume":"18","author":"Wasan","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.clon.2013.06.007","article-title":"Biological Consequences of Radiation-induced DNA Damage: Relevance to Radiotherapy","volume":"25","author":"Lomax","year":"2013","journal-title":"Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1080\/09553002.2020.1787544","article-title":"Combined radiation strategies for novel and enhanced cancer treatment","volume":"96","author":"Kareliotis","year":"2020","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_5","first-page":"330","article-title":"Nanoparticles in radiation therapy: A summary of various approaches to enhance radiosensitization in cancer","volume":"2","author":"Kwatra","year":"2013","journal-title":"Transl. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1080\/1061186X.2017.1400553","article-title":"Recent advances in metal nanoparticles in cancer therapy","volume":"26","author":"Sharma","year":"2018","journal-title":"J. Drug Target."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4830","DOI":"10.1039\/c2nr31227a","article-title":"Physical basis and biological mechanisms of gold nanoparticle radiosensitization","volume":"4","author":"Butterworth","year":"2012","journal-title":"Nanoscale"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chow, J. (2015). Characteristics of secondary electrons from irradiated gold nanoparticle in radiotherapy. Handbook of Nanoparticle, Springer.","DOI":"10.1007\/978-3-319-13188-7_10-1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12645-017-0026-0","article-title":"Biological mechanisms of gold nanoparticle radiosensitization","volume":"8","author":"Rosa","year":"2017","journal-title":"Cancer Nanotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tremi, I., Spyratou, E., Souli, M., Efstathopoulos, E.P., Makropoulou, M., Georgakilas, A.G., and Sihver, L. (2021). Requirements for Designing an Effective Metallic Nanoparticle (NP)-Boosted Radiation Therapy (RT). Cancers, 13.","DOI":"10.3390\/cancers13133185"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12645-019-0047-y","article-title":"Importance of radiolytic reactions during high-LET irradiation modalities: LET effect, role of O2 and radiosensitization by nanoparticles","volume":"10","author":"Baldacchino","year":"2019","journal-title":"Cancer Nanotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13268","DOI":"10.1038\/s41598-017-13736-y","article-title":"Interplay between the gold nanoparticle sub-cellular localization, size, and the photon energy for radiosensitization","volume":"7","author":"Lechtman","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pag\u00e1\u010dov\u00e1, E., \u0160tefan\u010d\u00edkov\u00e1, L., Schmidt-Kaler, F., Hildenbrand, G., Vi\u010dar, T., Depe\u0161, D., Lee, J.-H., Bestvater, F., Lacombe, S., and Porcel, E. (2019). Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030588"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"44752","DOI":"10.1038\/srep44752","article-title":"A mechanistic study of gold nanoparticle radiosensitisation using targeted microbeam irradiation","volume":"7","author":"Ghita","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"375101","DOI":"10.1088\/0957-4484\/20\/37\/375101","article-title":"Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle","volume":"20","author":"Roa","year":"2009","journal-title":"Nanotechnology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1080\/24701556.2020.1728553","article-title":"Gold nanoparticles induce G2\/M cell cycle arrest and enhance the expression of E-cadherin in breast cancer cells","volume":"50","author":"Mahfouz","year":"2020","journal-title":"Inorg. Nano-Met. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"285101","DOI":"10.1088\/0957-4484\/22\/28\/285101","article-title":"Thio-glucose bound gold nanoparticles enhance radio-cytotoxic targeting of ovarian cancer","volume":"22","author":"Geng","year":"2011","journal-title":"Nanotechnology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"295101","DOI":"10.1088\/0957-4484\/21\/29\/295101","article-title":"Evaluation of cytotoxicity and radiation enhancement using 1.9 nm gold particles: Potential application for cancer therapy","volume":"21","author":"Butterworth","year":"2010","journal-title":"Nanotechnology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1002\/smll.200900466","article-title":"Gold Nanoparticles of Diameter 1.4 nm Trigger Necrosis by Oxidative Stress and Mitochondrial Damage","volume":"5","author":"Pan","year":"2009","journal-title":"Small"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40514","DOI":"10.1039\/C5RA04013B","article-title":"BSA capped Au nanoparticle as an efficient sensitizer for glioblastoma tumor radiation therapy","volume":"5","author":"Chen","year":"2015","journal-title":"RSC Adv."},{"key":"ref_21","first-page":"415","article-title":"Gold nanoparticles enhance X-ray irradiation-induced apoptosis in head and neck squamous cell carcinoma in vitro","volume":"9","author":"Teraoka","year":"2018","journal-title":"Biomed. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8629","DOI":"10.1021\/nn202155y","article-title":"Gold Nanoparticles Induce Autophagosome Accumulation through Size-Dependent Nanoparticle Uptake and Lysosome Impairment","volume":"5","author":"Ma","year":"2011","journal-title":"ACS Nano"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10034","DOI":"10.3390\/ijms150610034","article-title":"Cytotoxic Autophagy in Cancer Therapy","volume":"15","author":"Sharma","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Xu, J., Elshazly, A.M., and Gewirtz, D.A. (2022). The Cytoprotective, Cytotoxic and Nonprotective Functional Forms of Autophagy Induced by Microtubule Poisons in Tumor Cells\u2014Implications for Autophagy Modulation as a Therapeutic Strategy. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071632"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/s12276-020-0455-4","article-title":"Autophagy as a decisive process for cell death","volume":"52","author":"Jung","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1017\/erm.2022.6","article-title":"Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair","volume":"24","author":"Nikitaki","year":"2022","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5993","DOI":"10.1088\/0031-9155\/61\/16\/5993","article-title":"Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol","volume":"61","author":"McNamara","year":"2016","journal-title":"Phys. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4944","DOI":"10.7150\/thno.42471","article-title":"Ultrasmall gold nanoparticles in cancer diagnosis and therapy","volume":"10","author":"Fan","year":"2020","journal-title":"Theranostics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.1088\/0031-9155\/55\/11\/004","article-title":"Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma","volume":"55","author":"Hainfeld","year":"2010","journal-title":"Phys. Med. Biol."},{"key":"ref_30","first-page":"271","article-title":"Nuclear Targeting of Gold Nanoparticles for Improved Therapeutics","volume":"16","author":"Celina","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5984","DOI":"10.1021\/acsami.5b00335","article-title":"Colloidally Stable and Surfactant-Free Protein-Coated Gold Nanorods in Biological Media","volume":"7","author":"Tebbe","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.addr.2015.12.012","article-title":"Gold nanoparticles for applications in cancer radiotherapy: Mechanisms and recent advancements","volume":"109","author":"Her","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s13404-011-0015-8","article-title":"Polyethylene glycol functionalized gold nanoparticles: The influence of capping density on stability in various media","volume":"44","author":"Manson","year":"2011","journal-title":"Gold Bull."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3712","DOI":"10.1021\/la00010a021","article-title":"Characterization of the Surface of a Citrate-Reduced Colloid Optimized for Use as a Substrate for Surface-Enhanced Resonance Raman Scattering","volume":"11","author":"Munro","year":"1995","journal-title":"Langmuir"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.rpor.2010.09.001","article-title":"A review on gold nanoparticles radiosensitization effect in radiation therapy of cancer","volume":"15","author":"Mesbahi","year":"2010","journal-title":"Rep. Pract. Oncol. Radiother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18044","DOI":"10.1038\/s41598-017-18304-y","article-title":"Radiosensitization of Prostate Cancers In Vitro and In Vivo to Erbium-filtered Orthovoltage X-rays Using Actively Targeted Gold Nanoparticles","volume":"7","author":"Khoo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Penninckx, S., Heuskin, A.-C., Michiels, C., and Lucas, S. (2020). Gold Nanoparticles as a Potent Radiosensitizer: A Transdisciplinary Approach from Physics to Patient. Cancers, 12.","DOI":"10.3390\/cancers12082021"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9407","DOI":"10.2147\/IJN.S272902","article-title":"Gold Nanoparticles as Radiosensitizers in Cancer Radiotherapy","volume":"15","author":"Chen","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00066-020-01576-1","article-title":"Assessment of DNA damage by 53PB1 and pKu70 detection in peripheral blood lymphocytes by immunofluorescence and high-resolution transmission electron microscopy","volume":"196","author":"Lorat","year":"2020","journal-title":"Strahlenther. Onkol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.dnarep.2015.01.007","article-title":"Nanoscale analysis of clustered DNA damage after high-LET irradiation by quantitative electron microscopy\u2014The heavy burden to repair","volume":"28","author":"Lorat","year":"2015","journal-title":"DNA Repair"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.dnarep.2011.01.012","article-title":"DNA repair in the context of chromatin: New molecular insights by the nanoscale detection of DNA repair complexes using transmission electron microscopy","volume":"10","author":"Lorat","year":"2011","journal-title":"DNA Repair"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.etap.2015.02.003","article-title":"In vitro cytotoxicity of gold nanorods in A549 cells","volume":"39","author":"Tang","year":"2015","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.colsurfb.2014.10.012","article-title":"Statistical analysis of gold nanoparticle-induced oxidative stress and apoptosis in myoblast (C2C12) cells","volume":"123","author":"Wahab","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1667\/RR3280","article-title":"Induction of Accelerated Senescence by \u03b3 Radiation in Human Solid Tumor-Derived Cell Lines Expressing Wild-Type TP53","volume":"163","author":"Razmik","year":"2005","journal-title":"Radiat. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7864","DOI":"10.1158\/0008-5472.CAN-07-6538","article-title":"Senescence-associated exosome release from human prostate cancer cells","volume":"68","author":"Lehmann","year":"2008","journal-title":"Cancer Res."},{"key":"ref_46","unstructured":"Demaria, M. (2019). A Novel Quantitative Method for the Detection of Lipofuscin, the Main By-Product of Cellular Senescence, in Fluids. Cellular Senescence: Methods and Protocols, Springer."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.21873\/invivo.12154","article-title":"A Novel Lipofuscin-detecting Marker of Senescence Relates With Hypoxia, Dysregulated Autophagy and With Poor Prognosis in Non-small-cell-lung Cancer","volume":"34","author":"Giatromanolaki","year":"2020","journal-title":"In Vivo"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/acel.12545","article-title":"Robust, universal biomarker assay to detect senescent cells in biological specimens","volume":"16","author":"Evangelou","year":"2017","journal-title":"Aging Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1039\/df9511100055","article-title":"A study of the nucleation and growth processes in the synthesis of colloidal gold","volume":"11","author":"Turkevich","year":"1951","journal-title":"Discuss. Faraday Soc."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Tremi, I., Havaki, S., Georgitsopoulou, S., Lagopati, N., Georgakilas, V., Gorgoulis, V.G., and Georgakilas, A.G. (2021). A Guide for Using Transmission Electron Microscopy for Studying the Radiosensitizing Effects of Gold Nanoparticles In Vitro. Nanomaterials, 11.","DOI":"10.3390\/nano11040859"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Tzani, M.A., Gabriel, C., and Lykakis, I.N. (2020). Selective Synthesis of Benzimidazoles from o-Phenylenediamine and Aldehydes Promoted by Supported Gold Nanoparticles. Nanomaterials, 10.","DOI":"10.3390\/nano10122405"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"14311","DOI":"10.1039\/c3ta13365f","article-title":"Mesoporous Au-TiO2 nanoparticle assemblies as efficient catalysts for the chemoselective reduction of nitro compounds","volume":"1","author":"Tamiolakis","year":"2013","journal-title":"J. Mater. Chem. A"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1365-2818.1992.tb03253.x","article-title":"An appraisal of low-temperature embedding by progressive lowering of temperature into Lowicryl HM20 for immunocytochemical studies","volume":"168","author":"Robertson","year":"1992","journal-title":"J. Microsc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1016\/j.bbamem.2016.04.001","article-title":"Gold nanoparticles in model biological membranes: A computational perspective","volume":"1858","author":"Rossi","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1039\/C6CS00636A","article-title":"Cellular uptake of nanoparticles: Journey inside the cell","volume":"46","author":"Behzadi","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.3762\/bjnano.5.174","article-title":"Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages","volume":"5","author":"Kuhn","year":"2014","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7606","DOI":"10.1016\/j.biomaterials.2010.06.051","article-title":"Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods","volume":"31","author":"Qiu","year":"2010","journal-title":"Biomaterials"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1186\/s11671-018-2728-6","article-title":"Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles","volume":"13","author":"Foroozandeh","year":"2018","journal-title":"Nanoscale Res. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1021\/ja4097384","article-title":"Structural Study of Citrate Layers on Gold Nanoparticles: Role of Intermolecular Interactions in Stabilizing Nanoparticles","volume":"136","author":"Park","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1021\/nl803054h","article-title":"Gold Nanoparticles Can Induce the Formation of Protein-based Aggregates at Physiological pH","volume":"9","author":"Zhang","year":"2009","journal-title":"Nano Lett."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Marques, A., Belchior, A., Silva, F., Marques, F., Campello, M.P.C., Pinheiro, T., Santos, P., Santos, L., Matos, A.P.A., and Paulo, A. (2022). Dose Rate Effects on the Selective Radiosensitization of Prostate Cells by GRPR-Targeted Gold Nanoparticles. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095279"},{"key":"ref_62","first-page":"210","article-title":"The dependence of radiation enhancement effect on the concentration of gold nanoparticles exposed to low- and high-LET radiations","volume":"31","author":"Liu","year":"2015","journal-title":"Phys. Med. Eur. J. Med. Phys."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Tabatabaie, F., Franich, R., Feltis, B., and Geso, M. (2022). Oxidative Damage to Mitochondria Enhanced by Ionising Radiation and Gold Nanoparticles in Cancer Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23136887"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3348","DOI":"10.1016\/j.febslet.2013.08.030","article-title":"ER stress suppresses DNA double-strand break repair and sensitizes tumor cells to ionizing radiation by stimulating proteasomal degradation of Rad51","volume":"587","author":"Yamamori","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.canlet.2014.02.005","article-title":"Radiosensitization of tumor cells through endoplasmic reticulum stress induced by PEGylated nanogel containing gold nanoparticles","volume":"347","author":"Yasui","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1667\/RR1984.1","article-title":"Gold Nanoparticles as Radiation Sensitizers in Cancer Therapy","volume":"173","author":"Chithrani","year":"2010","journal-title":"Radiat. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Igaz, N., Sz\u0151ke, K., Kov\u00e1cs, D., Buhala, A., Varga, Z., B\u00e9lteky, P., R\u00e1zga, Z., Tiszlavicz, L., Vizler, C., and Hidegh\u00e9ty, K. (2020). Synergistic Radiosensitization by Gold Nanoparticles and the Histone Deacetylase Inhibitor SAHA in 2D and 3D Cancer Cell Cultures. Nanomaterials, 10.","DOI":"10.3390\/nano10010158"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"675","DOI":"10.2147\/IJN.S226186","article-title":"Subcellular Performance of Nanoparticles in Cancer Therapy","volume":"15","author":"Liu","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Sun, H., Jia, J., Jiang, C., and Zhai, S. (2018). Gold Nanoparticle-Induced Cell Death and Potential Applications in Nanomedicine. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030754"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12989-017-0231-3","article-title":"Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface","volume":"14","author":"Durantie","year":"2017","journal-title":"Part. Fibre Toxicol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1007\/s11051-010-9911-8","article-title":"Toxicity and cellular uptake of gold nanoparticles: What we have learned so far?","volume":"12","author":"Alkilany","year":"2010","journal-title":"J. Nanoparticle Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1021\/acsomega.8b03227","article-title":"Identifying Trends in Gold Nanoparticle Toxicity and Uptake: Size, Shape, Capping Ligand, and Biological Corona","volume":"4","author":"Carnovale","year":"2019","journal-title":"ACS Omega"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1039\/c2cs15309b","article-title":"Endocytosis at the nanoscale","volume":"41","author":"Canton","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/jat.1486","article-title":"Cellular uptake and toxicity of gold nanoparticles in prostate cancer cells: A comparative study of rods and spheres","volume":"30","author":"Arnida","year":"2010","journal-title":"J. Appl. Toxicol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/ppsc.201300357","article-title":"The Cellular Interactions of PEGylated Gold Nanoparticles: Effect of PEGylation on Cellular Uptake and Cytotoxicity","volume":"31","author":"Soenen","year":"2014","journal-title":"Part. Part. Syst. Charact."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bromma, K., and Chithrani, D.B. (2020). Advances in Gold Nanoparticle-Based Combined Cancer Therapy. Nanomaterials, 10.","DOI":"10.3390\/nano10091671"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Liu, A.T., Cornejo, Y.R., Van Haute, D., and Berlin, J.M. (2020). A Systematic comparison of in vitro cell uptake and in vivo biodistribution for three classes of gold nanoparticles with saturated PEG coatings. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0234916"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1021\/nn800330a","article-title":"Uptake and Intracellular Fate of Surface-Modified Gold Nanoparticles","volume":"2","author":"Nativo","year":"2008","journal-title":"ACS Nano"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.nano.2014.12.016","article-title":"Targeted gold nanoparticles enhance sensitization of prostate tumors to megavoltage radiation therapy in vivo","volume":"11","author":"Wolfe","year":"2015","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"13015","DOI":"10.1021\/acsnano.9b05679","article-title":"Overcoming the Reticuloendothelial System Barrier to Drug Delivery with a \u201cDon\u2019t-Eat-Us\u201d Strategy","volume":"13","author":"Tang","year":"2019","journal-title":"ACS Nano"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Manzanares, D., and Ce\u00f1a, V. (2020). Endocytosis: The Nanoparticle and Submicron Nanocompounds Gateway into the Cell. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12040371"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/icb.2011.20","article-title":"Macropinocytosis: An endocytic pathway for internalising large gulps","volume":"89","author":"Lim","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.medengphy.2015.03.003","article-title":"Effects of particle uptake, encapsulation, and localization in cancer cells on intracellular applications","volume":"37","author":"Gal","year":"2015","journal-title":"Med. Eng. Phys."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6957","DOI":"10.2147\/IJN.S214008","article-title":"Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles","volume":"14","author":"Xia","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12645-020-00064-6","article-title":"Elucidating the fate of nanoparticles among key cell components of the tumor microenvironment for promoting cancer nanotechnology","volume":"11","author":"Bromma","year":"2020","journal-title":"Cancer Nanotechnol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Trono, J., Mizuno, K., Yusa, N., Matsukawa, T., and Uesaka, M. (2009, January 7\u201312). Cellular Uptake of Gold Nanoparticles into Normal and Cancer Cells. Proceedings of the World Congress on Medical Physics and Biomedical Engineering, Munich, Germany.","DOI":"10.1007\/978-3-642-03887-7_56"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1021\/nl070363y","article-title":"Elucidating the Mechanism of Cellular Uptake and Removal of Protein-Coated Gold Nanoparticles of Different Sizes and Shapes","volume":"7","author":"Chithrani","year":"2007","journal-title":"Nano Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1667\/0033-7587(2002)158[0657:LEEPRI]2.0.CO;2","article-title":"Low-Energy Electron Penetration Range in Liquid Water","volume":"158","author":"Meesungnoen","year":"2002","journal-title":"Radiat. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"19442","DOI":"10.1038\/srep19442","article-title":"Imaging and radiation effects of gold nanoparticles in tumour cells","volume":"6","author":"McQuaid","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"11647","DOI":"10.1039\/C7NR04620K","article-title":"Properties of in situ generated gold nanoparticles in the cellular context","volume":"9","author":"Drescher","year":"2017","journal-title":"Nanoscale"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Yan, H., Carlson, D.J., Abolfath, R., and Liu, W. (2021). Microdosimetric Investigation and a Novel Model of Radiosensitization in the Presence of Metallic Nanoparticles. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122191"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13014-018-1040-z","article-title":"The alfa and beta of tumours: A review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies","volume":"13","author":"Oei","year":"2018","journal-title":"Radiat. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1088\/0031-9155\/55\/4\/002","article-title":"Enhancement of cell radiation sensitivity by pegylated gold nanoparticles","volume":"55","author":"Liu","year":"2010","journal-title":"Phys. Med. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s10549-012-2338-4","article-title":"Molecularly targeted gold nanoparticles enhance the radiation response of breast cancer cells and tumor xenografts to X-radiation","volume":"137","author":"Chattopadhyay","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"12096","DOI":"10.1038\/s41598-020-68994-0","article-title":"Gold nanoparticle mediated radiation response among key cell components of the tumour microenvironment for the advancement of cancer nanotechnology","volume":"10","author":"Bromma","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12645-014-0005-7","article-title":"The role of mitochondrial function in gold nanoparticle mediated radiosensitisation","volume":"5","author":"Taggart","year":"2014","journal-title":"Cancer Nanotechnol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.ijrobp.2010.08.044","article-title":"Cell-Specific Radiosensitization by Gold Nanoparticles at Megavoltage Radiation Energies","volume":"79","author":"Jain","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.biopha.2013.04.003","article-title":"The role and mechanisms of nanoparticles to enhance radiosensitivity in hepatocellular cell","volume":"67","author":"Zheng","year":"2013","journal-title":"Biomed. Pharmacother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"20598","DOI":"10.1039\/C5RA26781A","article-title":"Biogenic gold nanoparticles induce cell cycle arrest through oxidative stress and sensitize mitochondrial membranes in A549 lung cancer cells","volume":"6","author":"Ramalingam","year":"2016","journal-title":"RSC Adv."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.radonc.2011.09.021","article-title":"A standardized G2-assay for the prediction of individual radiosensitivity","volume":"101","author":"Pantelias","year":"2011","journal-title":"Radiother. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.4161\/cc.22852","article-title":"p53 expression controls prostate cancer sensitivity to chemotherapy and the MDM2 inhibitor Nutlin-3","volume":"11","author":"Chappell","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.mad.2016.03.010","article-title":"Apoptosis or senescence? Which exit route do epithelial cells and fibroblasts preferentially follow?","volume":"156","author":"Georgakopoulou","year":"2016","journal-title":"Mech. Ageing Dev."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Elbakrawy, E., Kaur Bains, S., Bright, S., AL-Abedi, R., Mayah, A., Goodwin, E., and Kadhim, M. (2020). Radiation-Induced Senescence Bystander Effect: The Role of Exosomes. Biology, 9.","DOI":"10.3390\/biology9080191"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Nagineni, C.N., Naz, S., Choudhuri, R., Chandramouli, G.V.R., Krishna, M.C., Brender, J.R., Cook, J.A., and Mitchell, J.B. (2021). Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094835"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1667\/0033-7587(2001)155[0248:RISLGA]2.0.CO;2","article-title":"Radiation-Induced Senescence-Like Growth Arrest Requires TP53 Function but not Telomere Shortening","volume":"155","author":"Suzuki","year":"2001","journal-title":"Radiat. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.18632\/aging.100989","article-title":"Ionizing radiation-mediated premature senescence and paracrine interactions with cancer cells enhance the expression of syndecan 1 in human breast stromal fibroblasts: The role of TGF-\u03b2","volume":"8","author":"Liakou","year":"2016","journal-title":"Aging"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.15252\/embr.201439245","article-title":"Senescence and apoptosis: Dueling or complementary cell fates?","volume":"15","author":"Childs","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_108","first-page":"1470","article-title":"Tumor cell senescence, mitotic catastrophes, and their consequences","volume":"65","author":"Roninson","year":"2005","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/mutage\/gew052","article-title":"Impact of nanoparticles on DNA repair processes: Current knowledge and working hypotheses","volume":"32","author":"Carriere","year":"2016","journal-title":"Mutagenesis"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/pro6.1129","article-title":"Guidelines for radiotherapy of prostate cancer (2020 edition)","volume":"5","author":"Li","year":"2021","journal-title":"Precis. Radiat. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.21037\/tlcr-20-253","article-title":"Dose and fractionation schedules in radiotherapy for non-small cell lung cancer","volume":"10","author":"Kepka","year":"2020","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Milan, J., Niemczyk, K., and Kus-Li\u015bkiewicz, M. (2022). Treasure on the Earth-Gold Nanoparticles and Their Biomedical Applications. Materials, 15.","DOI":"10.3390\/ma15093355"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Boateng, F., and Ngwa, W. (2020). Delivery of Nanoparticle-Based Radiosensitizers for Radiotherapy Applications. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010273"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.2147\/IJN.S355142","article-title":"Multifunctional Gold Nanoparticles in Cancer Diagnosis and Treatment","volume":"17","author":"Yang","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3389\/fbioe.2019.00415","article-title":"Overcoming Physiological Barriers to Nanoparticle Delivery\u2014Are We There Yet?","volume":"7","author":"Thomas","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-med-040210-162544","article-title":"Nanoparticle Delivery of Cancer Drugs","volume":"63","author":"Wang","year":"2012","journal-title":"Annu. Rev. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/20\/5086\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:56:02Z","timestamp":1760144162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/20\/5086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":116,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cancers14205086"],"URL":"https:\/\/doi.org\/10.3390\/cancers14205086","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]}}}