Full-text resources of PSJD and other databases are now available in the new Library of Science.
Visit https://bibliotekanauki.pl


Preferences help
enabled [disable] Abstract
Number of results


2015 | 60 | 3 | 497-502

Article title

Synthesis and evaluation of radiolabeled, folic acid-PEG conjugated, amino silane coated magnetic nanoparticles in tumor bearing Balb/C mice


Title variants

Languages of publication



To design a potent agent for positron emission tomography/magnetic resonance imaging (PET/MRI) imaging and targeted magnetic hyperthermia-radioisotope cancer therapy radiolabeled surface modified superparamagnetic iron oxide nanoparticles (SPIONs) were used as nanocarriers. Folic acid was conjugated for increasing selective cellular binding and internalization through receptor-mediated endocytosis. SPIONs were synthesized by the thermal decomposition of tris (acetylacetonato) iron (III) to achieve narrow and uniform nanoparticles. To increase the biocompatibility of SPIONs, they were coated with (3-aminopropyl) triethoxysilane (APTES), and then conjugated with synthesized folic acid-polyethylene glycol (FA-PEG) through amine group of (3-aminopropyl) triethoxysilane. Finally, the particles were labeled with 64Cu (t1/2 = 12.7 h) using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono (N-hydroxy succinimide ester) DOTA-NHS chelator. After the characterization of SPIONs, their cellular internalization was evaluated in folate receptor (FR) overexpressing KB (established from a HeLa cell contamination) and mouse fibroblast cell (MFB) lines. Eventually, active and passive targeting effects of complex were assessed in KB tumor-bearing Balb/C mice through biodistribution studies. Synthesized bare SPIONs had low toxicity effect on healthy cells, but surface modification increased their biocompatibility. Moreover, KB cells viability was reduced when using folate conjugated SPIONs due to FR-mediated endocytosis, while having little effect on healthy cells (MFB). Moreover, this radiotracer had tolerable in vivo characteristics and tumor uptake. In the receptor blocked case, tumor uptake was decreased, indicating FR-specific uptake in tumor tissue while enhanced permeability and retention effect was major mechanism for tumor uptake.










Physical description


1 - 7 - 2015
1 - 6 - 2015
23 - 12 - 2014
6 - 8 - 2015


  • Department of Engineering, Garmsar Branch, Islamic Azad University, Garmsar, Iran, Tel.: +9891 0942 2335, Fax: 026 3446 4053
  • Department of Energy Engineering and Physics, Amirkabir University of Technology, Tehran, Iran
  • Young Researchers and Elite Club, South Tehran Branch, Islamic Azad University, Tehran, Iran
  • Biomedical Engineering Department, Science and Research Branch, Islamic Azad University, Tehran, Iran
  • Nuclear Medicine Research Group, Alborz Research Center, Karaj, Iran
  • Nuclear Engineering Department, East Tehran Branch, Islamic Azad University, Tehran, Iran


  • 1. Ting-Jung, C., Tsan-Hwang, C., Chiao-Y un, C., Sodio, C., & Hsu, N. (2009). Targeted herceptin-dextran iron oxide nanoparticles for noninvasive imaging of HER2/neu receptors using MRI. J. Biol. Inorg. Chem., 14, 253–260. DOI: 10.1007/s00775-008-0445-9.[WoS][Crossref]
  • 2. Brannon-Peppas, L., & Blanchette, J. O. (2012). Nanoparticle and targeted systems for cancer therapy. J. Adv. Drug Deliv. Rev., 64, 206–212. DOI: 10.1016/j.addr.2012.09.033.[WoS][Crossref]
  • 3. Guo, M., Que, C., Wang, C., Liu, X., Yan, H., & Liu, K. (2011). Multifunctional superparamagnetic nanocarriers with folate-mediated and pH-responsive targeting properties for anticancer drug delivery. Biomaterials, 32, 185–194. DOI: 10.1016/j.biomaterials.2010.09.077.[WoS][Crossref]
  • 4. Maeda, H., & Matsumura, Y. (1989). Tumouritropic and lymphotropic principles of macromolecular drugs. Crit. Rev. Ther. Drug Carr. System, 6, 193–210.
  • 5. Ohtsuka, N., Konno, T., Miyauchi, Y., & Maeda, H. (1987). Anticancer effects of arterial administration of the anticancer agent SMANCS with lipiodol on metastatic lymph nodes. Cancer, 59, 1560–1565. DOI: 10.1002/1097-0142(19870501)59:93.0.CO; 2-J.[Crossref]
  • 6. Feng, B., Hong, R. Y., Wang, L. S., Guoc, L., Li, H. Z., Dingd, J., Zhenge, Y., & Wei, D. G. (2008). Synthesis of Fe3O4/APTES/PEG diacid functionalized magnetic nanoparticles for MR imaging B. Colloid. Surf. A-Physicochem. Eng. Asp., 328, 52–59. DOI: 10.1016/j.colsurfa.2008.06.024.[Crossref]
  • 7. Yoo, M. K., Park, I. K., Lim, H. T., Lee, S. J., Jiang, H. L., Kim, Y. K., Choi, Y. J., Cho, M. H., & Cho, C. S. (2012). Folate-PEG-superparamagnetic iron oxide nanoparticles for lung cancer imaging. Acta Biomater., 8, 3005–3013. DOI: 10.1016/j.actbio.2012.04.029.[Crossref]
  • 8. Chem, T. J., Cheng, T. W., Hung, Y. C., Lin, K. T., Liu, G. C., & Wang, Y. M. (2008) Targeted folic acid-PEG nanoparticles for noninvasive imaging of folate receptor by MRI. J. Biomed. Mater. Res. Part A, 87, 165–75. DOI: 10.1002/jbm.a.31752.[WoS][Crossref]
  • 9. Sun, C., Sze, R., & Zhang, M. Q. (2006). Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI. J. Biomed. Mater. Res. Part A, 78(3), 550–557. DOI: 10.1002/jbm.a.30781.[Crossref]
  • 10. Walczak, P., Kedziorek, D. A., Gilad, A. A., Barnett, B. P., & Bulte, J. W. (2007). Applicability and limitations of MR tracking of neural stem cells with asymmetric cell division and rapid turnover. Magn. Reson. Med., 58, 261–269. DOI: 10.1002/mrm.21412.[Crossref][WoS]
  • 11. Montet, X., Montet-Abou, K., Reynolds, F., Weissleder, R., & Josephson, L. (2006). Nanoparticle imaging of integrins on tumor cells. Neoplasia, 8, 214–222. DOI: 10.1593/neo.05769.[Crossref]
  • 12. Lee, J. H., Huh, Y. M., Jun, Y. W., Seo, J. W., Jang, J. T., Song, H. T., Kim, S., Cho, E. J., Yoon, H. G., Suh, J. S., & Cheon, J. (2007). Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nat. Med., 13, 95–99. DOI: 10.1038/nm1467.[Crossref][WoS]
  • 13. Fukukawa, K., Rossin, R., Hagooly, A., Pressly, E. D., Hunt, J. N., Messmore, B. W., Wooley, K. L., Welch, M. J., & Hawker, C. J. (2008). Synthesis and characterization of core-shell star copolymers for in vivo PET imaging applications. Biomacromolecules, 9, 1329–1339. DOI: 10.1021/bm7014152.[Crossref]
  • 14. Rossin, R., Muro, S., Welch, M. J., Muzykantov, V. R., & Schuster, D. P. (2008). In vivo imaging of 64Cu-labeled polymer nanoparticles targeted to the lung endothelium. J. Nucl. Med., 49, 103–111. DOI: 10.2967/jnumed.107.045302.[Crossref]
  • 15. Sun, G., Hagooly, A., Xu, J., Nystrom, A. M., Li, Z., Rossin, R., Moore, D. A., Wooley, K. L., & Welch, M. J. (2008). Facile, efficient approach to accomplish tunable chemistries and variable biodistributions for shell crosslinked nanoparticles. Biomacromolecules, 9, 1997–2006. DOI: 10.1021/bm800246x.[WoS][Crossref]
  • 16. Sun, X., Rossin, R., Turner, J. L., Becker, M. L., Joralemon, M. J., Welch, M. J., & Wooley, K. L. (2005). An assessment of the effects of shell cross-linked nanoparticle size, core composition, and surface PEGylation on in vivo biodistribution. Biomacromolecules, 6, 2541–2554. DOI: 10.1021/bm050260e.[Crossref]
  • 17. Sun, X., & Anderson, C. (2004). Production and applications of copper-64 radiopharmaceuticals. Method. Enzymol., 386, 237–261. DOI: 10.1016/S0076-6879(04)86011-7.[Crossref]
  • 18. McCarthy, D., Shefer, R., Klinkowstein, R., Bass, L., Margeneau, W., Cutler, C., Anderson, C., & Welch, M. (1997). Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl. Med. Biol., 24, 35–43. DOI: 10.1016/S0969-8051(96)00157-6.[Crossref]
  • 19. McCarthy, D., Bass, L., Cutler, P., Shefer, R., Klinkowstein, R., Herrero, P., Lewis, J., Cutler, C., Anderson, C., & Welch, M. (1999). High purity production and potential applications of copper-60 and copper-61. Nucl. Med. Biol., 26, 351–358. DOI: 10.1016/S0969-8051(98)00113-9.[Crossref]
  • 20. Glaus, C., Rossin, R., Welch, M. J., & Gang, Bao (2010). In vivo evaluation of 64Cu-labeled magnetic nanoparticles as a dual-modality PET/MR imaging agent. Bioconjug. Chem., 21(4), 715–722. DOI: 10.1021/bc900511j.[Crossref]
  • 21. Heidari Majd, M., Asgari, D., Barara, J., Valizadeh, H., Kafil, V., Abadpour, A., Moumivand, E., Shahbazi Mojarrad, J., Rashidi, M. R., Coukos, G., & Omidi, Y. (2013). Tamoxifen loaded folic acid armed PEGylated magnetic nanoparticles for targeted imaging and therapy of cancer. J. Colloid. Surf. B-Biointerfaces, 106, 117–125. DOI: 10.1016/j.colsurfb.2013.01.051.[WoS][Crossref]
  • 22. Yang, X., Hong, H., Grailer, J. J., Rowland, I. J., Javadi, A., Hurley, S. A., Xiao, Y., Yang, Y., Zhang, Y., Nickles, R. J., Cai, W., Steeber, D. A., & Gonge, S. (2011). RGD-functionalized, DOX-conjugated, and 64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and SPECT/MR imaging. J. Biomater., 32(17), 4151–4160. DOI: 10.1016/j.biomaterials.2011.02.006.[Crossref]
  • 23. Xu, Z., Shen, C., Hou, Y., Gao, H., & Sun, S. (2009). Oleylamine as both reducing agent and stabilizer in a facile synthesis of magnetite nanoparticles. J. Chem. Mater., 21, 1778–1780. DOI: 10.1021/cm802978z.[Crossref][WoS]
  • 24. Xie, J., Xu, C., Xu, Z., Hou, Y., Young, K. L., Wang, S. X., Pourmand, N., & Sun, S. (2006). Linking hydrophilic macromolecules to monodisperse magnetite (Fe3O4) nanoparticles via trichloro-s-triazine. J. Chem. Mater., 18(3), 5401–5403. DOI: 10.1021/cm061793c.[Crossref]
  • 25. Müller, C., Forrer, F., & Schibli, R. (2008). SPECT study of folate receptor-positive malignant and normal tissues in mice using a novel 99mTc-radiofolate. J. Nucl. Med., 49, 310–317. DOI: 10.2967/jnumed.107.045856.[Crossref]
  • 26. Rossin, R., Pan, D., Qi, K., Turner, J. L., Sun, X., Wooley, K. L., & Welch, M. J. (2005). 64Cu-labeled folate-conjugated shell cross-linked nanoparticles for tumor imaging and radiotherapy: synthesis, radiolabeling, and biologic evaluation J. Nucl. Med., 46, 1210–1218.
  • 27. Zolata, H., Afarideh, H., & Abbasi-Davani, F. (2014). Radio-immunoconjugated, Dox-loaded, surface-modified superparamagnetic iron oxide nanoparticles (SPIONs) as a bioprobe for breast cancer tumor theranostics. J. Radioanal. Nucl. Chem., 301, 451–460. DOI: 10.1007/s10967-014-3101-6.[WoS][Crossref]

Document Type

Publication order reference


YADDA identifier

JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.