Sulforaphane Loaded PEGylated Iron Oxide-Gold Core Shell Nanoparticles: A Promising Delivery System for Cancer Therapy

  • Hamidreza Kheiri Manjili Department of Nanotechnology and Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University and School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
  • Leila Ma’mani Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran
  • Amir Izadi Young Researcher Club and Elite club, Islamic Azad University, East Tehran Branch, Tehran, Iran
  • Elham Moslemi Department of Biology, School of Basic Sciences, Islamic Azad University, East Tehran Branch, Tehran
  • Maedeh Mashhadikhan Departments of Biology, Faculty of Science, Tehran Science and Research Branch, Islamic Azad University, Tehran, Iran
  • Majid Mossahebi Mohammadi Departments of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  • ShararehTavaddod Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
  • Abbas Shafiee Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran
  • Hossein Naderi-Manesh Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Keywords: Apoptosis, Breast cancer, Cancer therapy, PEGylated gold-coated Fe3O4 nanoparticles, Sulforaphane


Herein we described a novel combination of sulforaphane (SF) with PEGylated gold coated Fe3O4 magnetic nanoparticles [(PEGylated Fe3O4@Au) NPs] to promote SF maintenance as an effective and promising anticancer drug. Physico-chemical properties of synthesized MNPs were assessed by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, vibrating sample magnetometery, dynamic light scattering, and Fourier transform infrared spectroscopy.


(a) Jurgons, R.; Seliger, C.; Hilpert, A.; Trahms, L.; Odenbach, S.; Alexiou, C., Drug loaded magnetic nanoparticles for cancer therapy. Journal of Physics: Condensed Matter 2006,18 (38), S2893;(b) Akhtar, J.; Siddiqui, H.; Fareed, S.; Aqil, M., Nanomulsion as a carrier for efficient delivery of metformin. Current drug delivery 2014,11 (2), 243-252.

Siddhartha, T.; Senthil, V.; Kishan, I.; Khatwal, R.; Madhunapantula, S., Design and Development of Oral Nanoparticulated Insulin in Multiple Emulsion. Current drug delivery 2014.

Tiash, S.; Othman, I.; Rosli, R.; Chowdhury, E., Methotrexate-and Cyclophosphamide-embedded Pure and Strontiumsubstituted Carbonate Apatite Nanoparticles for Augmentation of Chemotherapeutic Activities in Breast Cancer Cells. Current drug delivery 2014,11 (2), 214-222.

Huang, K.-S.; Shieh, D.; Yeh, C.; Wu, P.; Cheng, F., Antimicrobial Applications of Water-Dispersible Magnetic Nanoparticles in Biomedicine. Current medicinal chemistry 2014.

Su, X.; Zhan, X.; Tang, F.; Yao, J.; Wu, J., Magnetic nanoparticles in brain disease diagnosis and targeting drug delivery. Current Nanoscience 2011,7 (1), 37-46.

Salunkhe, A.; Khot, V.; Pawar, S., Magnetic Hyperthermia with Magnetic Nanoparticles: A Status Review. Current topics in medicinal chemistry 2014,14 (5), 572-594.

Schroeder, A.; Heller, D. A.; Winslow, M. M.; Dahlman, J. E.; Pratt, G. W.; Langer, R.; Jacks, T.; Anderson, D. G., Treating metastatic cancer with nanotechnology. Nature reviews. Cancer 2012,12 (1), 39-50.

(a) Zeng, L.; Ren, W.; Xiang, L.; Zheng, J.; Chen, B.; Wu, A., Multifunctional Fe3O4–TiO2 nanocomposites for magnetic resonance imaging and potential photodynamic therapy. Nanoscale 2013,5 (5), 2107-2113;(b) Li, X.; Zhao, D.; Zhang, F., Multifunctional upconversion-magnetic hybrid nanostructured materials: Synthesis and bioapplications. Theranostics 2013,3 (5), 292.

Goya, G.; Grazu, V.; Ibarra, M., Magnetic nanoparticles for cancer therapy. Current Nanoscience 2008,4 (1), 1-16.

Mao, R.; Wang, J.; Pei, J.; Wu, S.; Feng, J.; Lin, Y.; Cai, X., Pharmacokinetics and Applications of Magnetic Nanoparticles. Current drug metabolism 2013,14 (8), 872-878.

Mahmoud, W. E.; Bronstein, L. M.; Al-Hazmi, F.; Al-Noaiser, F.; Al-Ghamdi, A. A., Development of Fe/Fe3O4 Core–Shell Nanocubes as a Promising Magnetic Resonance Imaging Contrast Agent. Langmuir 2013,29 (42), 13095-13101.

Barreto, A.; Santiago, V.; Mazzetto, S.; Denardin, J.; Lavín, R.; Mele, G.; Ribeiro, M.; Vieira, I. G.; Gonçalves, T.; Ricardo, N., Magnetic nanoparticles for a new drug delivery system to control quercetin releasing for cancer chemotherapy. Journal of Nanoparticle Research 2011,13 (12), 6545-6553.

Kumar Prabhakar, P.; Vijayaraghavan, S.; Philip, J.; Doble, M., Biocompatibility studies of functionalized CoFe2O4 magnetic nanoparticles. Current Nanoscience 2011,7 (3), 371-376.

(a) Zhang, Y.; Talalay, P.; Cho, C.-G.; Posner, G. H., A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proceedings of the national academy of sciences 1992,89 (6), 2399-2403;(b) Cho, S. D.; Li, G.; Hu, H.; Jiang, C.; Kang, K. S.; Lee, Y. S.; Kim, S. H.; Lu, J., Involvement of c-Jun N-terminal kinase in G2/M arrest and caspase-mediated apoptosis induced by sulforaphane in DU145 prostate cancer cells. Nutrition and cancer 2005,52 (2), 213-24.

Do, D. P.; Pai, S. B.; Rizvi, S. A.; D'Souza, M. J., Development of sulforaphane-encapsulated microspheres for cancer epigenetic therapy. Int J Pharm 2010,386 (1-2), 114-21.

Jackson, S. J.; Singletary, K. W., Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. The Journal of nutrition 2004,134 (9), 2229-36.

(a) Lampe, J. W., Sulforaphane: from chemoprevention to pancreatic cancer treatment? Gut 2009,58 (7), 900-2;(b) Sutaria, D.; Grandhi, B. K.; Thakkar, A.; Wang, J.; Prabhu, S., Chemoprevention of pancreatic cancer using solid-lipid nanoparticulate delivery of a novel aspirin, curcumin and sulforaphane drug combination regimen. International journal of oncology 2012,41 (6), 2260-8.

(a) Kuroiwa, Y.; Nishikawa, A.; Kitamura, Y.; Kanki, K.; Ishii, Y.; Umemura, T.; Hirose, M., Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters. Cancer letters 2006,241 (2), 275-80;(b) Yang, C. S.; Wang, H.; Hu, B., Combination of chemopreventive agents in nanoparticles for cancer prevention. Cancer Prev Res (Phila) 2013,6 (10), 1011-4.

Jin, Y.; Wang, M.; Rosen, R. T.; Ho, C.-T., Thermal degradation of sulforaphane in aqueous solution. Journal of agricultural and food chemistry 1999,47 (8), 3121-3123.

Fauzia, V.; Umar, A. A.; Salleh, M. M.; Yahaya, M., Effect of Gold Nanoparticles Density Grown Directly on the Surface on the Performance of Organic Solar Cell. Current Nanoscience 2013,9 (2), 187-191.

(a) Ma, M.; Chen, H.; Chen, Y.; Wang, X.; Chen, F.; Cui, X.; Shi, J., Au capped magnetic core/mesoporous silica shell nanoparticles for combined photothermo-/chemo-therapy and multimodal imaging. Biomaterials 2012,33 (3), 989-998;(b) Liu, H.; Chen, D.; Li, L.; Liu, T.; Tan, L.; Wu, X.; Tang, F., Multifunctional gold nanoshells on silica nanorattles: a platform for the combination of photothermal therapy and chemotherapy with low systemic toxicity. Angewandte Chemie 2011,123 (4), 921-925;(c) Hui, C.; Shen, C.; Tian, J.; Bao, L.; Ding, H.; Li, C.; Tian, Y.; Shi, X.; Gao, H.-J., Core-shell Fe3O4@ SiO2 nanoparticles synthesized with well-dispersed hydrophilic Fe3O4 seeds. Nanoscale 2011,3 (2), 701-705;(d) Huff, T. B.; Tong, L.; Zhao, Y.; Hansen, M. N.; Cheng, J.-X.; Wei, A., Hyperthermic effects of gold nanorods on tumor cells. 2007;(e) Huang, X.; El-Sayed, I. H.; Qian, W.; El-Sayed, M. A., Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. Journal of the American Chemical Society 2006,128 (6), 2115-2120;(f) Ryou, S. M.; Kim, J. M.; Yeom, J. H.; Hyun, S.; Kim, S.; Han, M. S.; Kim, S. W.; Bae, J.; Rhee, S.; Lee, K., Gold nanoparticle-assisted delivery of small, highly structured RNA into the nuclei of human cells. Biochem Biophys Res Commun 2011,416 (1-2), 178-83.

Liang, J.; Zhou, Y.; Wu, J.; Ding, Y., Gold Nanoparticle-Based Drug Delivery Platform for Antineoplastic Chemotherapy. Current drug metabolism 2014.

Li, D.; Li, Q.; Hao, X.; Zhang, Y.; Zhang, Z.; Li, C., Assembled Core-Shell Nanostructures of Gold Nanoparticles with Biocompatible Polymers Toward Biology. Current topics in medicinal chemistry 2014,14 (5), 595-616.

Voliani, V.; Signore, G.; Nifosí, R.; Ricci, F.; Luin, S.; Beltram, F., Smart delivery and controlled drug release with gold nanoparticles: new frontiers in nanomedicine. Recent Patents on Nanomedicine 2012,2 (1), 34-44.

Alkilany, A. M.; Murphy, C. J., Toxicity and cellular uptake of gold nanoparticles: what we have learned so far? Journal of Nanoparticle Research 2010,12 (7), 2313-2333.

(a) Subramani, K.; Hosseinkhani, H.; Khraisat, A.; Hosseinkhani, M.; Pathak, Y., Targeting nanoparticles as drug delivery systems for cancer treatment. Current Nanoscience 2009,5 (2), 135-140;(b) Gupta, A. K.; Gupta, M., Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 2005,26 (18), 3995-4021;(c) Chen, M.; Yamamuro, S.; Farrell, D.; Majetich, S. A., Gold-coated iron nanoparticles for biomedical applications. Journal of applied physics 2003,93 (10), 7551-7553.

F Jiao, P.; Y Zhou, H.; X Chen, L.; Yan, B., Cancer-targeting multifunctionalized gold nanoparticles in imaging and therapy. Current medicinal chemistry 2011,18 (14), 2086-2102.

Barnett, C. M.; Gueorguieva, M.; Lees, M. R.; McGarvey, D. J.; Hoskins, C., Physical stability, biocompatibility and potential use of hybrid iron oxide-gold nanoparticles as drug carriers. Journal of Nanoparticle Research 2013,15 (6), 1-14.

M Joseph, M.; T Sreelekha, T., Gold Nanoparticles-Synthesis and Applications in Cancer Management. Recent Patents on Materials Science 2014,7 (1), 8-25.

Falahati, M.; Saboury, A. A.; Ma’mani, L.; Shafiee, A.; Rafieepour, H. A., The effect of functionalization of mesoporous silica nanoparticles on the interaction and stability of confined enzyme. International journal of biological macromolecules 2012,50 (4), 1048-1054.

Zhou, T.; Wu, B.; Xing, D., Bio-modified Fe3O4 core/Au shell nanoparticles for targeting and multimodal imaging of cancer cells. Journal of Materials Chemistry 2012,22 (2), 470-477.

Smolensky, E. D.; Neary, M. C.; Zhou, Y.; Berquo, T. S.; Pierre, V. C., Fe3O4@ organic@ Au: core–shell nanocomposites with high saturation magnetisation as magnetoplasmonic MRI contrast agents. Chemical Communications 2011,47 (7), 2149-2151.

Link, S.; El-Sayed, M. A., Size and temperature dependence of the plasmon absorption of colloidal gold nanoparticles. The Journal of Physical Chemistry B 1999,103 (21), 4212-4217.

Juge, N.; Mithen, R. F.; Traka, M., Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cellular and molecular life sciences : CMLS 2007,64 (9), 1105-27.

Lee, Y. R.; Noh, E. M.; Han, J. H.; Kim, J. M.; Hwang, B. M.; Kim, B. S.; Lee, S. H.; Jung, S. H.; Youn, H. J.; Chung, E. Y.; Kim, J. S., Sulforaphane controls TPA-induced MMP-9 expression through the NF-kappaB signaling pathway, but not AP-1, in MCF-7 breast cancer cells. BMB reports 2013,46 (4), 201-6.
Original Article