Original Articles

Increased Radiation Efficiency by Metal-Based Nanoparticles in Colorectal Cancer Cells

Abstract

Colorectal cancer (CRC) is diagnosed as one of the most prevalent cancers in the world. The application of radiotherapy in cancer treatment might be limited due to its radio resistance. Specific radiosensitizers are important factors in increasing the radiation therapy (RT) efficiency. In this study, Fe3O4@CuS-PEG nanoparticles in combination with the RT were evaluated for the treatment of CRC cells (HT-29 cells). HT-29 cells were treated with 2, 4, and 6 Gy of X-ray irradiation and/or a minimal toxic concentration of Fe3O4@CuS-PEG nanoparticles. The cytotoxic effect of various treatments was evaluated by MTT assay. Moreover, the malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and lactic acid level were assessed in single and combined treatments. Furthermore, the epidermal growth factor receptor (EGFR) gene expression level was measured by Quantitative Real-time PCR. Based on our results, cytotoxicity of Fe3O4@CuS-PEG nanoparticles was increased in a dose dependent manner. The nanoparticles were less cytotoxic in the concentration of 5 mg/mL compared to other examined concentrations. According to the results of MTT assay, the viability in the combined treatment groups was significantly lower than that of the single treatment groups. EGFR mRNA expression level was downregulated in radiation+nanoparticles groups in all examined doses of radiation. The level of MDA increased in the combined treatments compared to the alone treatments. Moreover, lactic acid level and SOD activity decreased in double agent combination treatments versus radiation alone. Based on our study, Fe3O4@CuS-PEG nanoparticles can be introduced as an effective radiosensitizer agent for targeted treatment of CRC cells. Moreover, combination treatment could efficiently treat cancerous cells and inhibit tumor growth in vitro.

1. Jalalian SH, Taghdisi SM, Shahidi Hamedani N, Kalat SA, Lavaee P, Zandkarimi M, et al. Epirubicin loaded super paramagnetic iron oxide nanoparticle-aptamer bioconjugate for combined colon cancer therapy and imaging in vivo. Eur J Pharm Sci 2013;50:191-7.
2. Mi Y, Shao Z, Vang J, Kaidar-Person O, Wang AZ. Application of nanotechnology to cancer radiotherapy. Cancer Nanotechnol 2016;7:11.
3. Barcellos-Hoff MH, Park C, Wright EG. Radiation and the microenvironment—tumorigenesis and therapy. Nat Rev Cancer 2005;5:867-75.
4. Bernier J, Hall EJ, Giaccia A. Radiation oncology: a century of achievements. Nat Rev Cancer 2004;4:737-47.
5. Zeng W, Liu C, Wang S, Wang Z, Huang Q. SnFe2O4 Nanozyme Based TME Improvement System for Anti-Cancer Combination Thermoradiotherapy. Front Oncol 2021;11:768829.
6. Li J, Shang W, Li Y, Fu S, Tian J, Lu L. Advanced nanomaterials targeting hypoxia to enhance radiotherapy. Int J Nanomedicine 2018;13:5925-36.
7. Huang Q, Zhang S, Zhang H, Han Y, Liu H, Ren F, et al. Boosting the Radiosensitizing and Photothermal Performance of Cu2–xSe Nanocrystals for Synergetic Radiophotothermal Therapy of Orthotopic Breast Cancer. ACS Nano 2019;13:1342-53.
8. Mohammadian M, Feizollahzadeh S, Mahmoudi R, Toofani Milani A, Rezapour-Firouzi S, Karimi Douna B. Hsp90 Inhibitor; NVP-AUY922 in Combination with Doxorubicin Induces Apoptosis and Downregulates VEGF in MCF-7 Breast Cancer Cell Line. Asian Pac J Cancer Prev 2020;21:1773-8.
9. Jafari S, Cheki M, Tavakoli MB, Zarrabi A, Ghazikhanlu Sani K, Afzalipour R. Investigation of Combination Effect Between 6 MV X-Ray Radiation and Polyglycerol Coated Superparamagnetic Iron Oxide Nanoparticles on U87-MG Cancer Cells. J Biomed Phys Eng 2020;10:15-24.
10. Wang H, Mu X, He H, Zhang XD. Cancer Radiosensitizers. Trends Pharmacol Sci 2018;39:24-48.
11. Fei W, Zhang M, Fan X, Ye Y, Zhao M, Zheng C, et al. Engineering of bioactive metal sulfide nanomaterials for cancer therapy. J Nanobiotechnology 2021;19:93.
12. Fu PP, Xia Q, Hwang HM, Ray PC, Yu H. Mechanisms of nanotoxicity: Generation of reactive oxygen species. J Food Drug Anal 2014;22:64-75.
13. Cuneo KC, Nyati MK, Ray D, Lawrence TS. EGFR targeted therapies and radiation: Optimizing efficacy by appropriate drug scheduling and patient selection. Pharmacol Ther 2015;154:67-77.
14. Arshad Z, Rezapour-Firouzi S, Mohammadian M, Ebrahimifar M. The Sources of Essential Fatty Acids for Allergic and Cancer Patients; a Connection with Insight into Mammalian Target of Rapamycin: A Narrative Review. Asian Pac J Cancer Prev 2018;19:2391-401.
15. Arshad Z, Rezapour-Firouzi S, Ebrahimifar M, Mosavi Jarrahi A, Mohammadian M. Association of Delta-6-Desaturase Expression with Aggressiveness of Cancer, Diabetes Mellitus, and Multiple Sclerosis: A Narrative Review. Asian Pac J Cancer Prev 2019;20:1005-18.
16. Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther 2021;6:201.
17. Ghader A, Gazestani AM, Minaei SE, Ardakani AA, Khoei S, Mohajer S, et al. Evaluation of nonlinear optical behavior of mouse colon cancer cell line CT26 in hyperthermia treatment. Lasers Med Sci 2019;34:1627-35.
18. Abelha TF, Neumann PR, Holthof J, Dreiss CA, Alexander C, Green M, et al. Low molecular weight PEG–PLGA polymers provide a superior matrix for conjugated polymer nanoparticles in terms of physicochemical properties, biocompatibility and optical/photoacoustic performance. J Mater Chem B 2019;7:5115-24.
19. Esgandari K, Mohammadian M, Zohdiaghdam R, Rastin SJ, Alidadi S, Behrouzkia Z. Combined treatment with silver graphene quantum dot, radiation, and 17-AAG induces anticancer effects in breast cancer cells. J Cell Physiol 2021;236:2817-28.
20. Gao Z, Liu X, Deng G, Zhou F, Zhang L, Wang Q, et al. Fe3O4@mSiO2-FA-CuS-PEG nanocomposites for magnetic resonance imaging and targeted chemo-photothermal synergistic therapy of cancer cells. Dalton Trans 2016;45:13456-65.
21. Meidanchi A. Mg (1-x) CuxFe2O4 superparamagnetic nanoparticles as nano-radiosensitizer agents in radiotherapy of MCF-7 human breast cancer cells. Nanotechnology 2020;31:325706.
22. Liu W, Chen B, Zheng H, Xing Y, Chen G, Zhou P, et al. Advances of Nanomedicine in Radiotherapy. Pharmaceutics 2021;13:1757.
23. Minaei SE, Mozdarani H, Motazakker M, Mansouri M, Aghamiri SM. Evaluation of cytogenetic alterations in peripheral blood lymphocytes of esophageal cancer patients treated with radiotherapy or chemoradiotherapy using cytokinesis-blocked micronucleus assay. Acta Med Iran 2016;54:9-14.
24. He C, Hu Y, Yin L, Tang C, Yin C. Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 2010;31:3657-66.
25. Alkhatib A, Watanabe Y, Broadhurst JH. The local enhancement of radiation dose from photons of MeV energies obtained by introducing materials of high atomic number into the treatment region. Med Phys 2009;36:3543-8.
26. Meidanchi A, Akhavan O, Khoei S, Shokri AA, Hajikarimi Z, Khansari N. ZnFe2O4 nanoparticles as radiosensitizers in radiotherapy of human prostate cancer cells. Mater Sci Eng C Mater Biol Appl 2015;46:394-9.
27. Klein S, Sommer A, Distel LV, Neuhuber W, Kryschi C. Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation. Biochem Biophys Res Commun 2012;425:393-7.
28. Rashid RA, Zainal Abidin S, Khairil Anuar MA, et al. Radiosensitization effects and ROS generation by high Z metallic nanoparticles on human colon carcinoma cell (HCT116) irradiated under 150 MeV proton beam. OpenNano 2019;4:100027.
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IssueVol 64 No 5 (2026) QRcode
SectionOriginal Articles
Keywords
Colorectal cancer Nanoparticle Radiation Epidermal growth factor receptor

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How to Cite
1.
Emamgholizadeh minaei S, Mohammadian M, Esnaashari O, Mostafanezhad K. Increased Radiation Efficiency by Metal-Based Nanoparticles in Colorectal Cancer Cells. Acta Med Iran. 2026;65(5):257-264.