Novel Synergistic Radiosensitization in Breast Cancer by Gold Nanoparticles and Curcumin: An In-Vitro Study
-
Kosar Esgandari
,
Reza Zohdiaghdam
,
Zhaleh Behrouzkia
,
Saleh Rouhi
,
Amirhossein Rashnoodi
,
Soroush Najafisarvestani
,
Ghazal Sadraei
Abstract
Background: Radiotherapy is a cornerstone of breast cancer (BC) treatment, but its efficacy is often limited by radioresistance and toxicity to adjacent healthy tissues. This study aimed to investigate, the novel synergistic radiosensitizing effects of combining gold nanoparticles (GNPs) and curcumin (CUR) with ionizing radiation on MCF-7 breast cancer cells.
Materials and Methods: MCF-7 (breast cancer) and L929 (healthy murine fibroblast) cells were treated with various concentrations of CUR and GNPs, alone and in combination, with and without radiation. Cytotoxicity was evaluated using the MTT assay, and dose-response curves were generated. The half-maximal inhibitory concentration (IC₅₀) of CUR was calculated via the median-effect equation using CompuSyn software. Lactate levels were measured using a Lactic Acid Assay Kit, and superoxide dismutase (SOD) enzyme activity was assessed by colorimetric method.
Results: CUR and GNPs both reduced cell viability in a dose-dependent manner, with MCF-7 cells showing significantly higher sensitivity than L929 cells. The combined treatment of CUR + GNPs + radiation exhibited a marked synergistic cytotoxic effect, significantly greater than any single or dual treatment (p < 0.05). This combination also induced apoptosis, substantially decreased lactate levels (indicating metabolic disruption), and reduced SOD activity in cancer cells.
Conclusion: The triple combination of gold nanoparticles, curcumin, and radiation demonstrates a novel and selective synergistic radiosensitizing effect against breast cancer cells while sparing normal cells.
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25- Dheeraj K Singh, Ramya Jagannathan, Puneet Khandelwal, Priya Mary Abraham, and Pankaj Poddar, "In situ synthesis and surface functionalization of gold nanoparticles with curcumin and their antioxidant properties: an experimental and density functional theory investigation." Nanoscale, Vol. 5 (No. 5), pp. 1882–93, (2013).
26- Vlad C Sandulache et al., "Acute tumor lactate perturbations as a biomarker of genotoxic stress: development of a biochemical model." Molecular cancer therapeutics, Vol. 14 (No. 12), pp. 2901–08, (2015).
27- Maedeh Yektamanesh, Yasin Ayyami, Marjan Ghorbani, Masoumeh Dastgir, Reza Malekzadeh, and Tohid Mortezazadeh, "Characterization of multifunctional β-cyclodextrin-coated Bi2O3 nanoparticles conjugated with curcumin for CT imaging-guided synergetic chemo-radiotherapy in breast cancer." International Journal of Pharmaceutics, Vol. 659p. 124264, (2024).
28- KE Sabitha and CS Shyamaladevi, "Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy." Oral Oncology, Vol. 35 (No. 3), pp. 273–77, (1999).
29- Yu Xia et al., "Microfluidic formulation of curcumin-loaded multiresponsive gelatin nanoparticles for anticancer therapy." ACS Biomaterials Science & Engineering, Vol. 9 (No. 6), pp. 3402–13, (2023).
30- Ke Yang et al., "Curcumin and glu‐GNPs induce radiosensitivity against breast cancer stem‐like cells." BioMed research international, Vol. 2020 (No. 1), p. 3189217, (2020).
31- Huiling Gu et al., "Design and Synthesis of Dimethylaminomethyl-Substituted Curcumin Derivatives: Potent Anti-Inflammatory, Anti-Oxidant, and Radioprotection Activity, Improved Aqueous Solubility Compared with Curcumin." Molecules, Vol. 29 (No. 9), p. 1985, (2024).
32- Ignasi Barba, Laura Carrillo-Bosch, and Joan Seoane, "Targeting the Warburg effect in cancer: where do we stand?" International journal of molecular sciences, Vol. 25 (No. 6), p. 3142, (2024).
33- Dingya Sun, Dun Hu, Jialu Wang, Xin Li, Jun Peng, and Shan Wang, "Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects." Nutrients, Vol. 18 (No. 1), p. 53, (2025).
34- Jiang Ni et al., "Nanomedicine-enabled disruption of glucose metabolism and synergistic antitumor therapy." Journal of Nanobiotechnology, Vol. 24 (No. 1), p. 253, (2026).
35- Zhino Moradi et al., "Anti-cancer effects of chemotherapeutic agent; 17-AAG, in combined with gold nanoparticles and irradiation in human colorectal cancer cells." DARU Journal of Pharmaceutical Sciences, Vol. 27 (No. 1), pp. 111–19, (2019).
36- Wei Li et al., "Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells." International journal of oncology, Vol. 52 (No. 5), pp. 1593–602, (2018).
37- Deep Kwatra, Anand Venugopal, and Shrikant Anant, "Nanoparticles in radiation therapy: a summary of various approaches to enhance radiosensitization in cancer." Translational Cancer Research, Vol. 2 (No. 4), (2013).
38- Jamileh Kadkhoda, Ali Tarighatnia, Jaleh Barar, Ayuob Aghanejad, and Soodabeh Davaran, "Recent advances and trends in nanoparticles based photothermal and photodynamic therapy." Photodiagnosis and photodynamic therapy, Vol. 37p. 102697, (2022).
39- Ali Tarighatnia et al., "Mucin-16 targeted mesoporous nano-system for evaluation of cervical cancer via dual-modal computed tomography and ultrasonography." New journal of chemistry, Vol. 45 (No. 40), pp. 18871–80, (2021).
40- Julie S Jurenka, "Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research." Alternative medicine review, Vol. 14 (No. 2), (2009).
41- Peng Zhao et al., "Potential roles and molecular mechanisms of bioactive ingredients in Curcumae Rhizoma against breast cancer." Phytomedicine, Vol. 114p. 154810, (2023).
2- Md Atiqur Rahman et al., "Advancements in breast cancer detection: A review of global Trends, risk Factors, imaging Modalities, machine learning, and deep learning approaches." BioMedInformatics, Vol. 5 (No. 3), p. 46, (2025).
3- George W Sledge, Eleftherios P Mamounas, Gabriel N Hortobagyi, Harold J Burstein, Pamela J Goodwin, and Antonio C Wolff, "Past, present, and future challenges in breast cancer treatment." Journal of Clinical Oncology, Vol. 32 (No. 19), pp. 1979–86, (2014).
4- Serguei A Castaneda and Jon Strasser, "Updates in the treatment of breast cancer with radiotherapy." Surgical Oncology Clinics, Vol. 26 (No. 3), pp. 371–82, (2017).
5- Chirag Shah, Zahraa Al-Hilli, and Frank Vicini, "Advances in breast cancer radiotherapy: implications for current and future practice." JCO oncology practice, Vol. 17 (No. 12), pp. 697–706, (2021).
6- Lars Erik Rutqvist, Carsten Rose, and Eva Cavallin-Ståhl, "A systematic overview of radiation therapy effects in breast cancer." Acta Oncologica, Vol. 42 (No. 5-6), pp. 532–45, (2003).
7- Parinaz Mehnati, Reza Malekzadeh, Mohammad Yousefi Sooteh, and Soheila Refahi, "Assessment of the efficiency of new bismuth composite shields in radiation dose decline to breast during chest CT." The Egyptian Journal of Radiology and Nuclear Medicine, Vol. 49 (No. 4), pp. 1187–89, (2018).
8- Nikan Asadpour, Reza Malekzadeh, Saeed Rajabpour, Soheila Refahi, Parinaz Mehnati, and Ahmad Shanei, "Shielding performance of multi-metal nanoparticle composites for diagnostic radiology: an MCNPX and Geant4 study." Radiological Physics and Technology, Vol. 16 (No. 1), pp. 57–68, (2023).
9- Parinaz Mehnati, Reza Malekzadeh, and Sooteh Mohammad Yousefi, "New Bismuth composite shield for radiation protection of breast during coronary CT angiography." Iranian journal of Radiology, Vol. 4 (No. 5 ), (2019).
10- Masoumeh Dastgir et al., "Synergistic radiosensitization of breast cancer using bismuth oxide nanoparticles coated with chitosan and β-cyclodextrin loaded with curcumin and 5-aminolevulinic acid." Cancer Nanotechnology, Vol. 17 (No. 1), p. 8, (2026).
11- Omid Talaee et al., "Characterization of a HER-2 targeted silica-gold nanoshells for breast cancer radio-photothermal therapy." Applied Radiation and Isotopes, p. 112454, (2026).
12- Reza Malekzadeh et al., "Dose enhancement by gold, iron oxide, bismuth oxide, and platinum nanoparticles in radiotherapy: a comprehensive meta-analysis." Radiological Physics and Technology, Vol. 19 (No. 2), pp. 479–98, (2026).
13- Haniye Ahrabi et al., "Dual-Purpose 5-Aminolevulinic Acid-Loaded Iron Oxide Nanoparticles: Enhancing Radiotherapy and MRI in Glioblastoma." Journal of Drug Delivery Science and Technology, p. 107853, (2025).
14- Haniye Ahrabi, Reza Malekzadeh, and Ghazale Geraily, "Application of 5-aminolevulinic acid in cancer radio-dynamic therapy: A systematic review." Radiation Physics and Chemistry, Vol. 236p. 112910, (2025).
15- Yasin Ayyami et al., "Characterization and application of targeted MnO2/CS@ ALA-MTX nano-radiosensitizers for boosting X-ray radiotherapy of brain tumors." Colloids and Surfaces A: Physicochemical and Engineering Aspects, Vol. 692p. 133975, (2024).
16- Saba Ziyaee, Reza Malekzadeh, Marjan Ghorbani, Behnam Nasiri Motlagh, Vahid Asghariazar, and Tohid Mortezazadeh, "Preparation of MnO2@ poly-(DMAEMA-co-IA)-conjugated methotrexate nano-complex for MRI and radiotherapy of breast cancer application." Magnetic Resonance Materials in Physics, Biology and Medicine, Vol. 36 (No. 5), pp. 779–95, (2023).
17- Bahman Alipour, Tohid Mortezazadeh, Waleed K Abdulsahib, Asghar Arzhang, Reza Malekzadeh, and Bagher Farhood, "A systematic review of multimodal application of quantum dots in breast cancer diagnosis: Effective parameters, status and future perspectives." Journal of Drug Delivery Science and Technology, Vol. 86p. 104682, (2023).
18- Reza Malekzadeh, Behnaz Babaye Abdollahi, Marjan Ghorbani, Jalil Pirayesh Islamian, and Tohid Mortezazadeh, "Trastuzumab conjugated PEG–Fe3O4@ Au nanoparticle as an MRI biocompatible nano-contrast agent." International Journal of Polymeric Materials and Polymeric Biomaterials, Vol. 72 (No. 10), pp. 759–70, (2023).
19- Reza Malekzadeh, Marjan Ghorbani, Parsa Faghani, Behnaz Babaye Abdollahi, Tohid Mortezazadeh, and Bagher Farhood, "Fabrication of targeted gold nanoparticle as potential contrast agent in molecular CT imaging." Journal of Radiation Research and Applied Sciences, Vol. 16 (No. 1), p. 100490, (2023).
20- Hedieh Mansouri et al., "A biocompatible theranostic nanoplatform based on magnetic gadolinium-chelated polycyclodextrin: in vitro and in vivo studies." Carbohydrate polymers, Vol. 254p. 117262, (2021).
21- Nolan Jackson, Daniel Cecchi, Wayne Beckham, and Devika B Chithrani, "Application of high-Z nanoparticles to enhance current radiotherapy treatment." Molecules, Vol. 29 (No. 11), p. 2438, (2024).
22- Behnaz Babaye Abdollahi, Marjan Ghorbani, Hamed Hamishehkar, Reza Malekzadeh, and Alireza Farajollahi, "Synthesis and characterization of actively HER-2 Targeted Fe3O4@ Au nanoparticles for molecular radiosensitization of breast cancer." BioImpacts: BI, Vol. 13 (No. 1), p. 17, (2022).
23- Joanna Kuzminska et al., "Curcumin derivatives in medicinal chemistry: potential applications in cancer treatment." Molecules, Vol. 29 (No. 22), p. 5321, (2024).
24- Khadija Akter, Kainat Gul, and Sohail Mumtaz, "Revisiting curcumin in cancer therapy: recent insights into molecular mechanisms, nanoformulations, and synergistic combinations." Current Issues in Molecular Biology, Vol. 47 (No. 9), p. 716, (2025).
25- Dheeraj K Singh, Ramya Jagannathan, Puneet Khandelwal, Priya Mary Abraham, and Pankaj Poddar, "In situ synthesis and surface functionalization of gold nanoparticles with curcumin and their antioxidant properties: an experimental and density functional theory investigation." Nanoscale, Vol. 5 (No. 5), pp. 1882–93, (2013).
26- Vlad C Sandulache et al., "Acute tumor lactate perturbations as a biomarker of genotoxic stress: development of a biochemical model." Molecular cancer therapeutics, Vol. 14 (No. 12), pp. 2901–08, (2015).
27- Maedeh Yektamanesh, Yasin Ayyami, Marjan Ghorbani, Masoumeh Dastgir, Reza Malekzadeh, and Tohid Mortezazadeh, "Characterization of multifunctional β-cyclodextrin-coated Bi2O3 nanoparticles conjugated with curcumin for CT imaging-guided synergetic chemo-radiotherapy in breast cancer." International Journal of Pharmaceutics, Vol. 659p. 124264, (2024).
28- KE Sabitha and CS Shyamaladevi, "Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy." Oral Oncology, Vol. 35 (No. 3), pp. 273–77, (1999).
29- Yu Xia et al., "Microfluidic formulation of curcumin-loaded multiresponsive gelatin nanoparticles for anticancer therapy." ACS Biomaterials Science & Engineering, Vol. 9 (No. 6), pp. 3402–13, (2023).
30- Ke Yang et al., "Curcumin and glu‐GNPs induce radiosensitivity against breast cancer stem‐like cells." BioMed research international, Vol. 2020 (No. 1), p. 3189217, (2020).
31- Huiling Gu et al., "Design and Synthesis of Dimethylaminomethyl-Substituted Curcumin Derivatives: Potent Anti-Inflammatory, Anti-Oxidant, and Radioprotection Activity, Improved Aqueous Solubility Compared with Curcumin." Molecules, Vol. 29 (No. 9), p. 1985, (2024).
32- Ignasi Barba, Laura Carrillo-Bosch, and Joan Seoane, "Targeting the Warburg effect in cancer: where do we stand?" International journal of molecular sciences, Vol. 25 (No. 6), p. 3142, (2024).
33- Dingya Sun, Dun Hu, Jialu Wang, Xin Li, Jun Peng, and Shan Wang, "Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects." Nutrients, Vol. 18 (No. 1), p. 53, (2025).
34- Jiang Ni et al., "Nanomedicine-enabled disruption of glucose metabolism and synergistic antitumor therapy." Journal of Nanobiotechnology, Vol. 24 (No. 1), p. 253, (2026).
35- Zhino Moradi et al., "Anti-cancer effects of chemotherapeutic agent; 17-AAG, in combined with gold nanoparticles and irradiation in human colorectal cancer cells." DARU Journal of Pharmaceutical Sciences, Vol. 27 (No. 1), pp. 111–19, (2019).
36- Wei Li et al., "Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells." International journal of oncology, Vol. 52 (No. 5), pp. 1593–602, (2018).
37- Deep Kwatra, Anand Venugopal, and Shrikant Anant, "Nanoparticles in radiation therapy: a summary of various approaches to enhance radiosensitization in cancer." Translational Cancer Research, Vol. 2 (No. 4), (2013).
38- Jamileh Kadkhoda, Ali Tarighatnia, Jaleh Barar, Ayuob Aghanejad, and Soodabeh Davaran, "Recent advances and trends in nanoparticles based photothermal and photodynamic therapy." Photodiagnosis and photodynamic therapy, Vol. 37p. 102697, (2022).
39- Ali Tarighatnia et al., "Mucin-16 targeted mesoporous nano-system for evaluation of cervical cancer via dual-modal computed tomography and ultrasonography." New journal of chemistry, Vol. 45 (No. 40), pp. 18871–80, (2021).
40- Julie S Jurenka, "Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research." Alternative medicine review, Vol. 14 (No. 2), (2009).
41- Peng Zhao et al., "Potential roles and molecular mechanisms of bioactive ingredients in Curcumae Rhizoma against breast cancer." Phytomedicine, Vol. 114p. 154810, (2023).
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How to Cite
1.
Esgandari K, Zohdiaghdam R, Behrouzkia Z, Rouhi S, Rashnoodi A, Najafisarvestani S, Sadraei G. Novel Synergistic Radiosensitization in Breast Cancer by Gold Nanoparticles and Curcumin: An In-Vitro Study. Frontiers Biomed Technol. 2026;.
