{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:00:29Z","timestamp":1789999229201,"version":"4.0.1"},"reference-count":66,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Cervical cancer treatment relies heavily on high-dose-rate (HDR) 192Ir brachytherapy; however, therapeutic efficacy remains limited by tumor radioresistance and the inability to escalate dose without increasing toxicity to surrounding healthy tissues. The present study investigates the potential of gold nanoparticles (AuNPs) to enhance radiosensitivity under clinically relevant 192Ir brachytherapy conditions through the combined action of physical dose amplification and radiobiological modulation. Particular emphasis is placed on the unique radiophysical interactions generated by the mixed gamma and secondary beta emissions of 192Ir, which, in the presence of high atomic number nanoparticles, promote localized photoelectric absorption and the emission of low-range secondary electrons, including Auger electrons. The study further aims to determine how AuNPs size and post-irradiation temporal evolution influence radiation-induced cytotoxicity and apoptosis in cervical cancer cell lines, thereby providing a biologically representative model of nanoparticle-assisted brachytherapy. Methods: Clonogenic survival, dose enhancement factor (DEF), and apoptosis were evaluated following irradiation in the presence of 10 nm and 50 nm AuNPs in two independent biological experiments (n = 2). Results: A clear dose-dependent reduction in survival fraction and increase in apoptosis were observed in nanoparticle-treated groups compared with irradiation alone. Radiosensitization demonstrated strong size dependence, with 50 nm AuNPs producing the greatest enhancement, a finding that may reflect size-dependent differences in cellular internalization, intracellular distribution, and nanoscale energy deposition previously established in AuNP studies. Importantly, biological effects intensified at later post-irradiation intervals, demonstrating a sustained temporal evolution of the radiobiological response beyond the initial irradiation event, potentially involving oxidative and other delayed cellular stress mechanisms described in AuNP radiosensitization. Conclusions: These findings demonstrate the capacity of AuNPs to enhance the radiobiological response of cervical cancer cells to 192Ir brachytherapy and identify nanoparticle size and post-irradiation time as important determinants of this effect. They therefore support AuNP-assisted brachytherapy as a promising strategy for further development toward biologically optimized radiotherapy capable of improving tumor response without escalation of the prescribed radiation dose.<\/jats:p>","DOI":"10.3390\/cancers18183025","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Gold Nanoparticles with Brachytherapy: In Vitro Insights into Radiosensitization in Cervical Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3296-3317","authenticated-orcid":false,"given":"Maria Anthi","family":"Kouri","sequence":"first","affiliation":[{"name":"Department of Applied Medical Physics, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Radiation Physics Materials Technology and Biomedical Imaging Laboratory (A\u039a\u03a4\u03a5BA), Department of Biomedical Engineering, University of West Attica, Egaleo, 12210 Athens, Greece"},{"name":"Medical Physics, General Hospital GHA Korgialeneio Mpenakeio-Hellenic Red Cross, 11526 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Maria-Eleni","family":"Kalkou","sequence":"additional","affiliation":[{"name":"Department of Applied Medical Physics, 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Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Flores-Balc\u00e1zar, C.H., Matsumoto-Palomares, S.A., Ch\u00e1vez-Zald\u00edvar, D.I., Marin-Trinidad, A.I., Castro-P\u00e9rez, F.G., and Cetina-P\u00e9rez, L.d.C. (2025). The Evolving Role of Radiation Oncology in the Management of Uterine Cervical Carcinoma: A State-of-the-Art Review for Non-Radiation Oncologists. Life, 15.","DOI":"10.3390\/life15121883"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2823","DOI":"10.15392\/2319-0612.2025.2823","article-title":"The Influence of Au, Gd and I Nanoparticles on Radiation Dose Absorption during High Dose Rate Brachytherapy with 192Ir Source","volume":"13","author":"Damian","year":"2025","journal-title":"Braz. J. Radiat. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"357","DOI":"10.21037\/tau.2017.12.08","article-title":"High dose-rate brachytherapy in the treatment of prostate cancer","volume":"7","author":"Mendez","year":"2018","journal-title":"Transl. Androl. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/S1470-2045(20)30753-1","article-title":"MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): A multicentre prospective cohort study","volume":"22","author":"Tanderup","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"213","DOI":"10.5114\/jcb.2025.153852","article-title":"Safety and efficacy of iridium-192 high-dose-rate interstitial brachytherapy for pleural and chest wall tumours: Preliminary results","volume":"17","author":"Zhang","year":"2025","journal-title":"J. Contemp. Brachyther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2300305","DOI":"10.1002\/adhm.202300305","article-title":"Gold-Enhanced Brachytherapy by a Nanoparticle-Releasing Hydrogel and 3D-Printed Subcutaneous Radioactive Implant Approach","volume":"12","author":"Kiseleva","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1021\/cbmi.3c00092","article-title":"Cancer Brachytherapy at the Nanoscale: An Emerging Paradigm","volume":"2","author":"Ghosh","year":"2024","journal-title":"Chem. Biomed. Imaging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103150","DOI":"10.1016\/j.mtbio.2026.103150","article-title":"Nanomaterials reshaping cancer radiotherapy: Radiosensitization mechanisms, delivery and theranostic platforms, multimodal synergy, and clinical translation strategies","volume":"38","author":"Liu","year":"2026","journal-title":"Mater. Today Bio"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4889","DOI":"10.1088\/0031-9155\/54\/16\/004","article-title":"The dosimetric feasibility of gold nanoparticle-aided radiation therapy (GNRT) via brachytherapy using low-energy gamma-\/x-ray sources","volume":"54","author":"Cho","year":"2009","journal-title":"Phys. Med. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4103\/jmp.jmp_86_21","article-title":"Calculation of Attenuation Parameter for Ir-192 Gamma Source in Shielding Materials","volume":"47","author":"Sabri","year":"2022","journal-title":"J. Med. Phys."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cooper, D.R., Bekah, D., and Nadeau, J.L. (2014). Gold nanoparticles and their alternatives for radiation therapy enhancement. Front. Chem., 2.","DOI":"10.3389\/fchem.2014.00086"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112637","DOI":"10.1016\/j.radphyschem.2025.112637","article-title":"Chemical mechanism in gold nanoparticles radiosensitization: A Monte Carlo simulation study","volume":"232","author":"Antunes","year":"2025","journal-title":"Radiat. Phys. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Schom\u00e4cker, K., Sudbrock, F., von Brandenstein, M.F., Akg\u00fcl, B., Hufbauer, M., Fischer, T., Sahnoun, S.E.M., Dietlein, F., Krapf, P., and Dietlein, M. (2026). Auger-Emitting Radionuclides in Radiopharmaceutical Research: Decay-Associated Processes, Vector-Dependent Localization, and Translational Perspectives. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27146445"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6533","DOI":"10.1088\/0031-9155\/55\/21\/013","article-title":"Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: Estimation of endothelial dose enhancement","volume":"55","author":"Ngwa","year":"2010","journal-title":"Phys. Med. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s00411-022-00989-z","article-title":"A matter of space: How the spatial heterogeneity in energy deposition determines the biological outcome of radiation exposure","volume":"61","author":"Baiocco","year":"2022","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2147\/IJN.S292105","article-title":"Effect of Gold Nanoparticle Radiosensitization on Plasmid DNA Damage Induced by High-Dose-Rate Brachytherapy","volume":"16","author":"Yogo","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nguyen, V.-K., Tsai, S.-W., Cho, I.-C., Chao, T.-C., Hsiao, I.-T., Huang, H.-C., and Liaw, J.-W. (2025). Gold Nanoparticle-Enhanced Production of Reactive Oxygen Species for Radiotherapy and Phototherapy. Nanomaterials, 15.","DOI":"10.3390\/nano15040317"},{"key":"ref_19","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 Nano"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41392-024-01839-8","article-title":"Mitochondrial dysfunction: Mechanisms and advances in therapy","volume":"9","author":"Zong","year":"2024","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_21","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_22","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_23","doi-asserted-by":"crossref","first-page":"e1701460","DOI":"10.1002\/adhm.201701460","article-title":"Gold Nanoparticles in Radiotherapy and Recent Progress in Nanobrachytherapy","volume":"7","author":"Fortin","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5604\/01.3001.0055.6432","article-title":"Gold Nanoparticles Functionalised with 197mHg\/197Hgfor Receptor-IndependentNanobrachytherapy of Triple-Negative Breast Cancer and Glioblastoma","volume":"22","author":"Majka","year":"2026","journal-title":"Bio-Algorithms Med.-Syst."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.3802\/jgo.2018.29.e86","article-title":"Treatment outcomes of high-dose-rate intracavitary brachytherapy for cervical cancer: A comparison of Ir-192 versus Co-60 sources","volume":"29","author":"Tantivatana","year":"2018","journal-title":"J. Gynecol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s13014-022-02170-8","article-title":"Radiobiological and dosimetric comparison of 60Co versus 192Ir high-dose-rate intracavitary-interstitial brachytherapy for cervical cancer","volume":"17","author":"Wen","year":"2022","journal-title":"Radiat. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"599472","DOI":"10.2147\/IJN.S599472","article-title":"Gold Nanoparticle Radiosensitization for High-Dose-Rate Brachytherapy: Differential Efficacy of PEG- and RGD-Functionalized Gold Nanoparticles Across 2-Dimensional, 3-Dimensional, and In Vivo Prostate Cancer Models","volume":"21","author":"Cecchi","year":"2026","journal-title":"Int. J. Nanomed."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e18006","DOI":"10.1002\/mp.18006","article-title":"Radiotherapeutic efficacy of gold nanoparticles for high dose-rate brachytherapy compared to conventional radiotherapy: An in vitro study","volume":"52","author":"Cecchi","year":"2025","journal-title":"Med. Phys."},{"key":"ref_29","unstructured":"ATCC (2026, April 21). SiHa\u2014HTB-35. Available online: https:\/\/www.atcc.org\/products\/htb-35."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.1002\/mp.16454","article-title":"Multiscale Monte Carlo simulations of gold nanoparticle dose-enhanced radiotherapy I: Cellular dose enhancement in microscopic models","volume":"50","author":"Martinov","year":"2023","journal-title":"Med. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12645-016-0021-x","article-title":"Gold nanoparticles for cancer radiotherapy: A review","volume":"7","author":"Haume","year":"2016","journal-title":"Cancer Nanotechnol."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","unstructured":"Tremi, I., Havaki, S., Georgitsopoulou, S., Terzoudi, G., Lykakis, I.N., Iliakis, G., Georgakilas, V., Gorgoulis, V.G., and Georgakilas, A.G. (2022). Biological Response of Human Cancer Cells to Ionizing Radiation in Combination with Gold Nanoparticles. Cancers, 14.","DOI":"10.3390\/cancers14205086"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.7150\/thno.15019","article-title":"Standards and Methodologies for Characterizing Radiobiological Impact of High-Z Nanoparticles","volume":"6","author":"Subiel","year":"2016","journal-title":"Theranostics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1021\/nl052396o","article-title":"Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells","volume":"6","author":"Chithrani","year":"2006","journal-title":"Nano Lett."},{"key":"ref_36","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_37","doi-asserted-by":"crossref","unstructured":"Yogo, K., Misawa, M., Shimizu, H., Kitagawa, T., Hirayama, R., Ishiyama, H., Yasuda, H., Kametaka, S., and Takami, S. (2022). Radiosensitization Effect of Gold Nanoparticles on Plasmid DNA Damage Induced by Therapeutic MV X-rays. Nanomaterials, 12.","DOI":"10.3390\/nano12050771"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kerr, B.N., Duffy, D., McInerney, C.E., Hutchinson, A., Dabaja, I., Bazzi, R., Roux, S., Prise, K.M., and Butterworth, K.T. (2023). Evaluation of Radiosensitization and Cytokine Modulation by Differentially PEGylated Gold Nanoparticles in Glioblastoma Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210032"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5733","DOI":"10.2147\/IJN.S174624","article-title":"Determination of dose enhancement caused by AuNPs with Xoft\u00ae Axxent\u00ae Electronic (eBxTM) and conventional brachytherapy: In vitro study","volume":"13","author":"Shahhoseini","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"64","DOI":"10.30574\/gscarr.2021.7.1.0043","article-title":"Fundamental characteristics and application of radiation","volume":"7","author":"Karmaker","year":"2021","journal-title":"GSC Adv. Res. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Vlastou, E., Pantelis, E., Efstathopoulos, E.P., Karaiskos, P., Kouloulias, V., and Platoni, K. (2022). Quantification of Nanoscale Dose Enhancement in Gold Nanoparticle-Aided External Photon Beam Radiotherapy. Cancers, 14.","DOI":"10.3390\/cancers14092167"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Akhdar, H., Alanazi, R., Alanazi, N., and Alodhayb, A. (2022). Secondary Electrons in Gold Nanoparticle Clusters and Their Role in Therapeutic Ratio: The Outcome of a Monte Carlo Simulation Study. Molecules, 27.","DOI":"10.3390\/molecules27165290"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"504001","DOI":"10.1088\/1361-6528\/aae272","article-title":"A gold nanoparticle system for enhancement of radiotherapy and simultaneous monitoring of reactive-oxygen-species formation","volume":"29","author":"Choi","year":"2018","journal-title":"Nanotechnology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1021\/acsnanomed.5c00110","article-title":"Tumor Radiosensitization with Gold Nanoparticles: Evolving Strategies to Improve Tumoral Gold Uptake and Catalyze Future Clinical Translation","volume":"1","author":"Biswal","year":"2026","journal-title":"ACS Nano Med."},{"key":"ref_46","unstructured":"Teles, P., Dias, C., Belo, J.H., Sousa, C., Boaventura, P., Bravo, I., Santos, J., and Rylander, M. (2025). Monte Carlo Simulation and Dosimetric Analysis of Gold Nanoparticles (AuNPs) in Breast Tissue. arXiv."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"14346","DOI":"10.1038\/s41598-019-50861-2","article-title":"Radio-enhancement effects by radiolabeled nanoparticles","volume":"9","author":"Gholami","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Li, W.B., Bernal, M.A., and Francis, Z. (2026). Range of dose enhancement factor for gold nanoparticles in radiotherapy using Monte Carlo simulations. Radiat. Environ. Biophys., 1\u201329.","DOI":"10.1007\/s00411-026-01245-4"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Nickoloff, J.A., Sharma, N., and Taylor, L. (2020). Clustered DNA Double-Strand Breaks: Biological Effects and Relevance to Cancer Radiotherapy. Genes, 11.","DOI":"10.3390\/genes11010099"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13014-026-02907-9","article-title":"FLASH radiotherapy: Physico-chemical considerations on ionisation tracks, radical reactions, and the role of oxygen","volume":"21","author":"Herskind","year":"2026","journal-title":"Radiat. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2011.12.012","article-title":"Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury","volume":"327","author":"Azzam","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"100126","DOI":"10.1016\/j.nucana.2024.100126","article-title":"Gold nanoparticle effect on dose and DNA damage enhancement in the vicinity of gold nanoparticles","volume":"3","author":"Bardane","year":"2024","journal-title":"Nucl. Anal."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Jin, Y., Zhu, J., Yang, Y., Li, Z., and Qin, Y. (2026). Oxidative Stress-Guided Gold Nanoparticles for Cancer Theranostics. Antioxidants, 15.","DOI":"10.3390\/antiox15050641"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1002\/mp.17676","article-title":"Monte Carlo study of gold nanoparticle-mediated radiosensitization effects using nanoscale cell model combined with fractal-based DNA model","volume":"52","author":"Kaphle","year":"2025","journal-title":"Med. Phys."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Koushki, K., Biswal, P., Vijay, G.V., Sadeghi, M., Dehnavi, S., Tra, N.T., Samala, S.K., Yousefi Taba, M., Vasan, A.B., and Han, E. (2025). Immunomodulatory Effects of Gold Nanoparticles: Impacts on Immune Cells and Mechanisms of Action. Nanomaterials, 15.","DOI":"10.3390\/nano15151201"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41420-020-00314-x","article-title":"Small size gold nanoparticles enhance apoptosis-induced by cold atmospheric plasma via depletion of intracellular GSH and modification of oxidative stress","volume":"6","author":"Jawaid","year":"2020","journal-title":"Cell Death Discov."},{"key":"ref_57","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_58","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1021\/acs.bioconjchem.7b00252","article-title":"Gold Nanoparticle Size and Shape Effects on Cellular Uptake and Intracellular Distribution of siRNA Nanoconstructs","volume":"28","author":"Yue","year":"2017","journal-title":"Bioconjug Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kouri, M.A., Tsaroucha, A., Axakali, T.-M., Varelas, P., Kouloulias, V., Platoni, K., and Efstathopoulos, E.P. (2025). Targeting Cancer Cell Fate: Apoptosis, Autophagy, and Gold Nanoparticles in Treatment Strategies. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47060460"},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"100080","DOI":"10.1016\/j.preme.2026.100080","article-title":"Mitochondria-targeted nanoplatforms for tumor therapy: Design principles, applications, challenges and prospects","volume":"3","author":"Zhao","year":"2026","journal-title":"Precis. Med. Eng."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Enea, M., Pereira, E., Peixoto de Almeida, M., Ara\u00fajo, A.M., Bastos, M.d.L., and Carmo, H. (2020). Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells. Nanomaterials, 10.","DOI":"10.3390\/nano10050995"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"111778","DOI":"10.1016\/j.jphotobiol.2020.111778","article-title":"Size-dependent apoptotic activity of gold nanoparticles on osteosarcoma cells correlated with SERS signal","volume":"203","author":"Chakraborty","year":"2020","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e70573","DOI":"10.1002\/mp.70573","article-title":"Radiobiology studies of gold nanoparticle-enhanced radiosensitization in proton therapy","volume":"53","author":"Esperante","year":"2026","journal-title":"Med. Phys."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Engelbrecht-Roberts, M., Miles, X., Vandevoorde, C., and de Kock, M. (2025). An Evaluation of the Potential Radiosensitization Effect of Spherical Gold Nanoparticles to Induce Cellular Damage Using Different Radiation Qualities. Molecules, 30.","DOI":"10.3390\/molecules30051038"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Kouri, M.A., Spyratou, E., Kalkou, M.-E., Patatoukas, G., Angelopoulou, E., Tremi, I., Havaki, S., Gorgoulis, V.G., Kouloulias, V., and Platoni, K. (2023). Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines. 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