Skip to main content Skip to main navigation menu Skip to site footer

Cytotoxicity of curcumin-loaded magnetic nanoparticles against normal and cancer cells as a breast cancer drug delivery system

  • Ali Mollaie Ghanat Alnooj
  • Melika Ghobadi
  • Mohammad Mousavi-Khattat
  • Dina Zohrabi
  • Mohammad Sekhavati
  • Ali Zarrabi


Recently, therapeutic applications of modified magnetic nanoparticles have attracted the attention of many researchers. The reason is the ability to develop nano drugs as cancer treatment agents. For this purpose, these particles must have a tiny size, intrinsic magnetic properties, imaging effectiveness, the ability to target the drug, and high drug absorption. Although studies have been performed on the anti-cancer properties of curcumin/nanoparticles, no comprehensive research has been performed to evaluate its anti-cancer and the normal cell toxicity of this drug system for breast cancer treatment. This study designed a curcumin-loaded MNPs (MNPs@CUR) formulation to accomplish these unique features. Using the diffusion process, chemical precipitation was used to make MNPs, which were then loaded with curcumin (CUR). Transmission electron microscopy (TEM) was used to study the morphology and size of MNP-CUR. The fabricated MNPs had spherical shapes with an average length of 23.22 nm. The presence of curcumin on the surface of MNPs was approved using Fourier transform infrared (FTIR) analysis. The X-ray diffraction (XRD) diffractogram confirmed the face cubic center (fcc) character of MNPs.  After 24 hours of incubation with 4t1 breast cancer cells, MNPs@CUR anticancer effects were evaluated. MNPs@CUR displayed a concentration-dependent preference for applying anticancer effects on 4t1cells (IC50=108 µg/ml).  Separated in vivo anti-tumor studies of coated/naked nanoparticles and curcumin also demonstrated that MNPs@CUR eliminated tumor mass. The cytotoxicity and genotoxicity against normal peripheral blood mononuclear cells (PBMC) were also measured by 2,5-diphenyl-2H-tetrazolium bromide (MTT) electrophoresis DNA digestion methods respectively for MNPs@CUR and naked MNPs. Cytotoxicity was demonstrated at high concentrations of MNP@CUR (991 µg/ml), while naked nanoparticles showed approximately no toxicity and neither had genotoxicity.



  1. Abdallah, F. M., Helmy, M. W., Katary, M. A., & Ghoneim, A. I. J. N.-S. s. a. o. p. (2018). Synergistic antiproliferative effects of curcumin and celecoxib in hepatocellular carcinoma HepG2 cells. 391(12), 1399-1410.
  2. Abotaleb, M., Kubatka, P., Caprnda, M., Varghese, E., Zolakova, B., Zubor, P., . . . Pharmacotherapy. (2018). Chemotherapeutic agents for the treatment of metastatic breast cancer: An update. 101, 458-477.
  3. Aguilera, G., Berry, C. C., West, R. M., Gonzalez-Monterrubio, E., Angulo-Molina, A., Arias-Carrión, Ó., & Méndez-Rojas, M. Á. J. N. A. (2019). Carboxymethyl cellulose coated magnetic nanoparticles transport across a human lung microvascular endothelial cell model of the blood–brain barrier. 1(2), 671-685.
  4. Ak, G., Yilmaz, H., Güneş, A., Hamarat Sanlier, S. J. A. c., nanomedicine,, & biotechnology. (2018). In vitro and in vivo evaluation of folate receptor-targeted a novel magnetic drug delivery system for ovarian cancer therapy. 46(sup1), 926-937.
  5. Ali, M., & Smiley, R. J. T. F. J. (2018). Curcumin Induces Apoptosis via the Capase‐8 Activated Extrinsic Pathway in MDA‐MB‐231 Breast Cancer Cells. 32, 664.666-664.666.
  6. Almaki, J. H., Nasiri, R., Idris, A., Majid, F. A. A., Salouti, M., Wong, T. S., . . . Amini, N. (2016). Synthesis, characterization and in vitro evaluation of exquisite targeting SPIONs–PEG–HER in HER2+ human breast cancer cells. Nanotechnology, 27(10), 105601.
  7. Arsalani, S., Guidelli, E. J., Silveira, M. A., Salmon, C. E., Araujo, J. F., Bruno, A. C., . . . Materials, M. (2019). Magnetic Fe3O4 nanoparticles coated by natural rubber latex as MRI contrast agent. 475, 458-464.
  8. Asab, G., Zereffa, E. A., & Abdo Seghne, T. J. I. j. o. b. (2020). Synthesis of silica-coated Fe3O4 nanoparticles by microemulsion method: characterization and evaluation of antimicrobial activity. 2020.
  9. Bai, Y., An, N., Chen, D., Liu, Y.-z., Liu, C.-p., Yao, H., . . . Tian, W. J. C. P. (2020). Facile construction of shape-regulated β-cyclodextrin-based supramolecular self-assemblies for drug delivery. 231, 115714.
  10. Baki, A., Remmo, A., Löwa, N., Wiekhorst, F., & Bleul, R. J. I. J. o. M. S. (2021). Albumin-coated single-core iron oxide nanoparticles for enhanced molecular magnetic imaging (Mri/mpi). 22(12), 6235.
  11. Bakshi, S., Zakharchenko, A., Minko, S., Kolpashchikov, D. M., & Katz, E. J. M. (2019). Towards nanomaterials for cancer theranostics: a system of DNA-modified magnetic nanoparticles for detection and suppression of RNA marker in cancer cells. 5(2), 24.
  12. Betsou, F., Gaignaux, A., Ammerlaan, W., Norris, P. J., & Stone, M. (2019). Biospecimen Science of Blood for Peripheral Blood Mononuclear Cell (PBMC) Functional Applications. Current Pathobiology Reports, 7(2), 17-27. doi:10.1007/s40139-019-00192-8
  13. Brenner, D. R., Weir, H. K., Demers, A. A., Ellison, L. F., Louzado, C., Shaw, A., . . . Smith, L. M. J. C. (2020). Projected estimates of cancer in Canada in 2020. 192(9), E199-E205.
  14. Bu, L. L., Rao, L., Yu, G. T., Chen, L., Deng, W. W., Liu, J. F., . . . Zhao, X. Z. J. A. F. M. (2019). Cancer stem cell‐platelet hybrid membrane‐coated magnetic nanoparticles for enhanced photothermal therapy of head and neck squamous cell carcinoma. 29(10), 1807733.
  15. Chenthamara, D., Subramaniam, S., Ramakrishnan, S. G., Krishnaswamy, S., Essa, M. M., Lin, F.-H., & Qoronfleh, M. W. (2019). Therapeutic efficacy of nanoparticles and routes of administration. Biomaterials Research, 23(1), 20. doi:10.1186/s40824-019-0166-x
  16. Cianfruglia, L., Minnelli, C., Laudadio, E., Scirè, A., & Armeni, T. J. A. (2019). Side effects of curcumin: Epigenetic and antiproliferative implications for normal dermal fibroblast and breast cancer cells. 8(9), 382.
  17. Council, N. R. (2010). Guide for the care and use of laboratory animals.
  18. D'Angelo, N. A., Noronha, M. A., Kurnik, I. S., Câmara, M. C., Vieira, J. M., Abrunhosa, L., . . . Ataide, J. A. J. I. J. o. P. (2021). Curcumin encapsulation in nanostructures for cancer therapy: A 10-year overview. 604, 120534.
  19. Dabagh, S., Chaudhary, K., Haris, S. A., Haider, Z., & Ali, J. (2018). Aluminium Substituted Ferrite Nanoparticles with Enhanced Antibacterial Activity. Journal of Computational and Theoretical Nanoscience, 15(3), 1052-1058.
  20. Desreux, J. A. J. E. j. o. o., gynecology, & biology, r. (2018). Breast cancer screening in young women. 230, 208-211.
  21. Dutta, B., Shelar, S. B., Rajan, V., Checker, S., Divya, Barick, K. C., . . . Hassan, P. A. (2022). Gelatin grafted Fe3O4 based curcumin nanoformulation for cancer therapy. Journal of Drug Delivery Science and Technology, 67, 102974. doi:
  22. Dutta, P., Sarkissyan, M., Paico, K., Wu, Y., Vadgama, J. V. J. B. c. r., & treatment. (2018). MCP-1 is overexpressed in triple-negative breast cancers and drives cancer invasiveness and metastasis. 170(3), 477-486.
  23. Finnegan, M. T. V., Herbert, K. E., Evans, M. D., Griffiths, H. R., & Lunec, J. (1996). Evidence for sensitisation of DNA to oxidative damage during isolation. Free Radical Biology and Medicine, 20(1), 93-98. doi:
  24. Fratantonio, D., Molonia, M. S., Bashllari, R., Muscarà, C., Ferlazzo, G., Costa, G., . . . Speciale, A. J. P. (2019). Curcumin potentiates the antitumor activity of Paclitaxel in rat glioma C6 cells. 55, 23-30.
  25. Fu, S., Li, G., Zang, W., Zhou, X., Shi, K., & Zhai, Y. J. A. P. S. B. (2021). Pure drug nano-assemblies: A facile carrier-free nanoplatform for efficient cancer therapy.
  26. Galli, M., Guerrini, A., Cauteruccio, S., Thakare, P., Dova, D., Orsini, F., . . . Licandro, E. (2017). Superparamagnetic iron oxide nanoparticles functionalized by peptide nucleic acids. RSC Adv., 7, 15500-15512. doi:10.1039/C7RA00519A
  27. George Kallivalappil, G., & Kuttan, G. J. I. (2019). Efficacy of punarnavine in restraining organ-specific tumour progression in 4T1-induced murine breast tumour model. 27(4), 701-712.
  28. Gómez-Archila, L. G., Palomino-Schätzlein, M., Zapata-Builes, W., & Galeano, E. J. P. o. (2021). Development of an optimized method for processing peripheral blood mononuclear cells for 1H-nuclear magnetic resonance-based metabolomic profiling. 16(2), e0247668.
  29. Guney Eskiler, G., Sahin, E., Deveci Ozkan, A., Cilingir Kaya, O. T., Kaleli, S. J. N., & Cancer. (2020). Curcumin induces DNA damage by mediating homologous recombination mechanism in triple negative breast cancer. 72(6), 1057-1066.
  30. Hassanzadeh-Afruzi, F., Dogari, H., Esmailzadeh, F., & Maleki, A. (2021). Magnetized melamine-modified polyacrylonitrile (PAN@melamine/Fe3O4) organometallic nanomaterial: Preparation, characterization, and application as a multifunctional catalyst in the synthesis of bioactive dihydropyrano [2,3-c]pyrazole and 2-amino-3-cyano 4H-pyran derivatives. 35(10), e6363. doi:
  31. Hwang, J.-h., Jeong, H., Jung, Y.-o., Nam, K. T., & Lim, K.-M. (2021). Skin irritation and inhalation toxicity of biocides evaluated with reconstructed human epidermis and airway models. Food and Chemical Toxicology, 150, 112064. doi:
  32. Jayachandran, A., T R, A., & Nair, A. (2021). Green synthesis and characterization of zinc oxide nanoparticles using Cayratia pedata leaf extract. Biochemistry and Biophysics Reports, 26, 100995. doi:10.1016/j.bbrep.2021.100995
  33. Justin, C., Samrot, A. V., Sahithya, C. S., Bhavya, K. S., & Saipriya, C. J. P. O. (2018). Preparation, characterization and utilization of coreshell super paramagnetic iron oxide nanoparticles for curcumin delivery. 13(7), e0200440.
  34. Khan, A. Q., Ahmed, E. I., Elareer, N., Fathima, H., Prabhu, K. S., Siveen, K. S., . . . Ahmad, A. J. I. j. o. m. s. (2020). Curcumin-mediated apoptotic cell death in papillary thyroid cancer and cancer stem-like cells through targeting of the JAK/STAT3 signaling pathway. 21(2), 438.
  35. Lee, W.-H., Loo, C.-Y., Rohanizadeh, R. J. M. S., & C, E. (2019). Functionalizing the surface of hydroxyapatite drug carrier with carboxylic acid groups to modulate the loading and release of curcumin nanoparticles. 99, 929-939.
  36. Lopez-Barbosa, N., Suárez-Arnedo, A., Cifuentes, J., Gonzalez Barrios, A. F., Silvera Batista, C. A., Osma, J. F., . . . Engineering. (2019). Magnetite–OmpA Nanobioconjugates as Cell-Penetrating Vehicles with Endosomal Escape Abilities. 6(1), 415-424.
  37. Mehdinia, A., Mirzaeipour, R., & Jabbari, A. (2019). Nanosized Fe3O4–curcumin conjugates for adsorption of heavy metals from seawater samples. Journal of the Iranian Chemical Society, 16(7), 1431-1439. doi:10.1007/s13738-019-01619-0
  38. Mousavi-Khattat, M., Keyhanfar, M., & Razmjou, A. (2018). A comparative study of stability, antioxidant, DNA cleavage and antibacterial activities of green and chemically synthesized silver nanoparticles. Artif Cells Nanomed Biotechnol, 46(sup3), S1022-s1031. doi:10.1080/21691401.2018.1527346
  39. Nam, K. C., Han, Y. S., Lee, J.-M., Kim, S. C., Cho, G., & Park, B. J. J. C. (2020). Photo-functionalized magnetic nanoparticles as a nanocarrier of photodynamic anticancer agent for biomedical theragnostics. 12(3), 571.
  40. Nasiri, R., Dabagh, S., Meamar, R., Idris, A., Muhammad, I., Irfan, M., & Nodeh, H. R. (2020). Papain grafted into the silica coated iron-based magnetic nanoparticles ‘IONPs@ SiO2-PPN’as a new delivery vehicle to the HeLa cells. Nanotechnology, 31(19), 195603.
  41. Nguyen, N. Y., Luong, H. V. T., Pham, D. T., Tran, T. B. Q., & Dang, H. G. (2022). Chitosan-functionalized Fe3O4@SiO2 nanoparticles as a potential drug delivery system. Chemical Papers, 76(7), 4561-4570. doi:10.1007/s11696-022-02189-x
  42. Nigjeh, S. E., Yeap, S. K., Nordin, N., Rahman, H., & Rosli, R. J. M. (2019). In vivo anti-tumor effects of citral on 4T1 breast cancer cells via induction of apoptosis and downregulation of aldehyde dehydrogenase activity. 24(18), 3241.
  43. Nosrati, H., Salehiabar, M., Attari, E., Davaran, S., Danafar, H., & Manjili, H. K. J. A. O. C. (2018). Green and one‐pot surface coating of iron oxide magnetic nanoparticles with natural amino acids and biocompatibility investigation. 32(2), e4069.
  44. O’Meara, T., Marczyk, M., Qing, T., Yaghoobi, V., Blenman, K., Cole, K., . . . Pusztai, L. J. J. P. O. (2020). Immunological differences between immune-rich estrogen receptor–positive and immune-rich triple-negative breast cancers. 3, 767-779.
  45. Oroujeni, M., Kaboudin, B., Xia, W., Jönsson, P., & Ossipov, D. A. J. P. i. O. C. (2018). Conjugation of cyclodextrin to magnetic Fe3O4 nanoparticles via polydopamine coating for drug delivery. 114, 154-161.
  46. Osorio Jaimes, M. J. (2020). Produced water demulsification using maghemite nanoparticles.
  47. Ostroverkhov, P., Semkina, A., Naumenko, V., Plotnikova, E., Melnikov, P., Abakumova, T., . . . science, i. (2019). Synthesis and characterization of bacteriochlorin loaded magnetic nanoparticles (MNP) for personalized MRI guided photosensitizers delivery to tumor. 537, 132-141.
  48. Palesh, O., Scheiber, C., Kesler, S., Mustian, K., Koopman, C., & Schapira, L. J. T. b. j. (2018). Management of side effects during and post‐treatment in breast cancer survivors. 24(2), 167-175.
  49. Pan, R., Zeng, Y., Liu, G., Wei, Y., Xu, Y., & Tao, L. J. P. C. (2020). Curcumin–polymer conjugates with dynamic boronic acid ester linkages for selective killing of cancer cells. 11(7), 1321-1326.
  50. Patra, S., Pradhan, B., Nayak, R., Behera, C., Rout, L., Jena, M., . . . Bhutia, S. K. (2021). Chemotherapeutic efficacy of curcumin and resveratrol against cancer: Chemoprevention, chemoprotection, drug synergism and clinical pharmacokinetics. Paper presented at the Seminars in cancer biology.
  51. Rekha, S., & Anila, E. J. M. L. (2019). In vitro cytotoxicity studies of surface modified CaS nanoparticles on L929 cell lines using MTT assay. 236, 637-639.
  52. Roychoudhury, S., Chakraborty, S., Das, A., Guha, P., Agarwal, A., & Henkel, R. (2021). Herbal medicine use to treat andrological problems: Asian and Indian subcontinent: Ginkgo biloba, Curcuma longa, and Camellia sinensis. In (pp. 129-146).
  53. Septisetyani, E., Santoso, A., Wisnuwardhani, P., & Prasetyaningrum, P. (2020). Cytotoxic effects of chemopreventive agents curcumin, naringin and epigallocathecin-3-gallate in C2C12 myoblast cells. Paper presented at the IOP Conference Series: Earth and Environmental Science.
  54. Shah, M., Murad, W., Mubin, S., Ullah, O., Rehman, N. U., & Rahman, M. H. (2022). Multiple health benefits of curcumin and its therapeutic potential. Environmental Science and Pollution Research, 29(29), 43732-43744. doi:10.1007/s11356-022-20137-w
  55. Sun, H., Zhang, B., Jiang, X., Liu, H., Deng, S., Li, Z., & Shi, H. J. N. (2019). Radiolabeled ultra-small Fe3O4 nanoprobes for tumor-targeted multimodal imaging. 14(1), 5-17.
  56. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 71(3), 209-249. doi:
  57. Tian, X., Ruan, L., Zhou, S., Wu, L., Cao, J., Qi, X., . . . Shen, S. (2022). Appropriate Size of Fe3O4 Nanoparticles for Cancer Therapy by Ferroptosis. ACS Applied Bio Materials, 5(4), 1692-1699. doi:10.1021/acsabm.2c00068
  58. Wang, D., Zhu, K., Tian, J., Li, Z., Du, G., Guo, Q., . . . Biology. (2018). Clinicopathological and ultrasonic features of triple-negative breast cancers: a comparison with hormone receptor-positive/human epidermal growth factor receptor-2-negative breast cancers. 44(5), 1124-1132.
  59. Wu, L., Zong, L., Ni, H., Liu, X., Wen, W., Feng, L., . . . Shen, S. J. B. s. (2019). Magnetic thermosensitive micelles with upper critical solution temperature for NIR triggered drug release. 7(5), 2134-2143.
  60. Yusefi, M., Shameli, K., & Jumaat, A. F. J. J. o. A. R. i. M. S. (2020). Preparation and properties of magnetic iron oxide nanoparticles for biomedical applications: A brief review. 75(1), 10-18.
  61. Zoi, V., Galani, V., Vartholomatos, E., Zacharopoulou, N., Tsoumeleka, E., Gkizas, G., . . . Leonardos, I. J. B. (2021). Curcumin and Radiotherapy Exert Synergistic Anti-Glioma Effect In Vitro. 9(11), 1562.

How to Cite

Alnooj, A. M. G. ., Ghobadi, M. ., Mousavi-Khattat, M. ., Zohrabi, D. ., Sekhavati, M. ., & Zarrabi, A. . (2022). Cytotoxicity of curcumin-loaded magnetic nanoparticles against normal and cancer cells as a breast cancer drug delivery system. Nanofabrication, 7.


289 17


Search Panel


Article Details

Most Read This Month


Copyright (c) 2022 Ali Mollaie Ghanat Alnooj, Melika Ghobadi, Mohammad Mousavi-Khattat, Dina Zohrabi, Mohammad Sekhavati, Ali Zarrabi

Creative Commons License

This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Most read articles by the same author(s)

  • Alisa Khodadadi, Atefeh Zarepour, Sepideh Abbaszadeh, Maryam Firoozi, Fatemeh Bahrami-Banan, Amir Rabiee, Mahnaz Hassanpour, Mehraneh Kermanian, Samiramis Pourmotabed, Ali Zarrabi, Omid Moradi, Sepideh Yousefiasl, Alireza Iranbakhsh, Seyed Mohammadreza Mirkhan, Ehsan Nazarzadeh Zare, Matineh Ghomi, Saeed Beigi-Boroujeni, Ana Cláudia Paiva-Santos, Yasser Vasseghian, Pooyan Makvandi, Esmaeel Sharifi, Nanotechnology for SARS-CoV-2 diagnosis , Nanofabrication: Vol. 7 (2022): Nanofabrication