Nano Research

, Volume 10, Issue 9, pp 3212–3227 | Cite as

Folate targeted coated SPIONs as efficient tool for MRI

  • Cinzia Scialabba
  • Roberto Puleio
  • Davide Peddis
  • Gaspare Varvaro
  • Pietro Calandra
  • Giovanni Cassata
  • Luca Cicero
  • Mariano Licciardi
  • Gaetano Giammona
Research Article

Abstract

The development of more sensitive diagnostic tools allowing an early-stage and highly efficient medical imaging of tumors remains a challenge. Magnetic nanoparticles seem to be the contrast agents with the highest potential, if properly constructed. Therefore, in this study, hybrid magnetic nanoarchitectures were developed using a new amphiphilic inulin-based graft copolymer (INU-LAPEG-FA) as coating material for 10-nm spinel iron oxide (magnetite, Fe3O4) superparamagnetic nanoparticles (SPION). Folic acid (FA) covalently linked to the coating copolymer in order to be exposed onto the nanoparticle surface was chosen as the targeting agent because folate receptors are upregulated in many cancer types. Physicochemical characterization and in vitro biocompatibility study was then performed on the prepared magnetic nanoparticles. The improved targeting and imaging properties of the prepared FA-SPIONs were further evaluated in nude mice using 7-Tesla magnetic resonance imaging (MRI). FA-SPIONs exhibited the ability to act as efficient contrast agents in conventional MRI, providing a potential nanoplatform not only for tumor diagnosis but also for cancer treatment, through the delivery of anticancer drug or locoregional magnetic hyperthermia.

Keywords

inulin copolymer superparamagnetic spinel iron oxide nanoparticles (SPIONs) magnetic resonance imaging (MRI) folic acid (FA) cancer targeting 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

12274_2017_1540_MOESM1_ESM.pdf (828 kb)
Folate targeted coated SPIONs as efficient tool for MRI

References

  1. [1]
    Bakhtiary, Z.; Saei, A. A.; Hajipour, M. J.; Raoufi, M.; Vermesh, O.; Mahmoudi, M. Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges. Nanomedicine 2016, 12, 287–307.CrossRefGoogle Scholar
  2. [2]
    Liu, X. L.; Ng, C. T.; Chandrasekharan, P.; Yang, H. T.; Zhao, L. Y.; Peng, E.; Lv, Y. B.; Xiao, W.; Fang, J.; Yi, J. B. et al. Synthesis of ferromagnetic Fe0.6Mn0.4O nanoflowers as a new class of magnetic theranostic platform for in vivo T 1T 2 dual-mode magnetic resonance imaging and magnetic hyperthermia therapy. Adv. Healthc. Mater. 2016, 5, 2092–2104.CrossRefGoogle Scholar
  3. [3]
    Lee, N.; Yoo, D.; Ling, D. S.; Cho, M. H.; Hyeon, T.; Cheon, J. Iron oxide based nanoparticles for multimodal imaging and magnetoresponsive therapy. Chem. Rev. 2015, 115, 10637–10689.CrossRefGoogle Scholar
  4. [4]
    Sharifi, S.; Seyednejad, H.; Laurent, S.; Atyabi, F.; Saei, A. A.; Mahmoudi, M. Superparamagnetic iron oxide nanoparticles for in vivo molecular and cellular imaging. Contrast Media Mol. I. 2015, 10, 329–355.CrossRefGoogle Scholar
  5. [5]
    Li, J. C.; He, Y.; Sun, W. J.; Luo, Y.; Cai, H. D.; Pan, Y. Q.; Shen, M. W.; Xia, J. D.; Shi, X. Y. Hyaluronic acid-modified hydrothermally synthesized iron oxide nanoparticles for targeted tumor MRimaging. Biomaterials 2014, 35, 3666–3677.CrossRefGoogle Scholar
  6. [6]
    Zhang, Z. X.; Hu, Y.; Yang, J.; Xu, Y. H.; Zhang, C. Z.; Wang, Z. L.; Shi, X. Y.; Zhang, G. X. Facile synthesis of folic acid-modified iron oxide nanoparticles for targeted MRimaging in pulmonary tumor xenografts. Mol. Imaging Biol. 2016, 18, 569–578.CrossRefGoogle Scholar
  7. [7]
    Scialabba, C.; Licciardi, M.; Mauro, N.; Rocco, F.; Ceruti, M.; Giammona, G. Inulin-based polymer coated SPIONs as potential drug delivery systems for targeted cancer therapy. Eur. J. Pharm. Biopharm. 2014, 88, 695–705.CrossRefGoogle Scholar
  8. [8]
    Berry, C. C.; Wells, S.; Charles, S.; Aitchison, G.; Curtis, A. S. G. Cell response to dextran-derivatised iron oxide nanoparticles post internalisation. Biomaterials 2004, 25, 5405–5413.CrossRefGoogle Scholar
  9. [9]
    Kohler, N.; Sun, C.; Fichtenholtz, A.; Gunn, J.; Fang, C.; Zhang, M. Q. Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery. Small 2006, 2, 785–792.CrossRefGoogle Scholar
  10. [10]
    Licciardi, M.; Li Volsi, A.; Sardo, C.; Mauro, N.; Cavallaro, G.; Giammona, G. Inulin-ethylenediamine coated SPIONs magnetoplexes: A promising tool for improving siRNA delivery. Pharm. Res. 2015, 32, 3674–3687.CrossRefGoogle Scholar
  11. [11]
    Namgung, R.; Singha, K.; Yu, M. K.; Jon, S.; Kim, Y. S.; Ahn, Y.; Park, I. K.; Kim, W. J. Hybrid superparamagnetic iron oxide nanoparticle-branched polyethylenimine magnetoplexes for gene transfection of vascular endothelial cells. Biomaterials 2010, 31, 4204–4213.CrossRefGoogle Scholar
  12. [12]
    Licciardi, M.; Scialabba, C.; Cavallaro, G.; Sangregorio, C.; Fantechi, E.; Giammona, G. Cell uptake enhancement of folate targeted polymer coated magnetic nanoparticles. J. Biomed. Nanotechnol. 2013, 9, 949–964.CrossRefGoogle Scholar
  13. [13]
    Licciardi, M.; Scialabba, C.; Fiorica, C.; Cavallaro, G.; Cassata, G.; Giammona, G. Polymeric nanocarriers for magnetic targeted drug delivery: Preparation, characterization, and in vitro and in vivo evaluation. Mol. Pharmaceutics 2013, 10, 4397–4407.CrossRefGoogle Scholar
  14. [14]
    Laurent, S.; Saei, A. A.; Behzadi, S.; Panahifar, A.; Mahmoudi, M. Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: Opportunities and challenges. Expert Opin. Drug Deliv. 2014, 11, 1449–1470.CrossRefGoogle Scholar
  15. [15]
    Wang, Y.-X. J. Superparamagnetic iron oxide based MRI contrast agents: Current status of clinical application. Quant. Imaging Med. Surg. 2011, 1, 35–40.Google Scholar
  16. [16]
    Mauro, N.; Li Volsi, A.; Scialabba, C.; Licciardi, M.; Cavallaro, G.; Giammona, G. Photothermal ablation of cancer cells using folate-coated gold/grapheme oxide composite. Curr. Drug Deliv., in press, DOI: 10.2174/ 1567201813666160520113804.Google Scholar
  17. [17]
    Licciardi, M.; Li Volsi, A.; Mauro, N.; Scialabba, C.; Cavallaro, G.; Giammona G., Preparation and characterization of inulin coated gold nanoparticles for selective delivery of doxorubicin to breast cancer cells. J. Nanomater. 2016, 2016, 2078315.CrossRefGoogle Scholar
  18. [18]
    Sardo, C.; Craparo, E. F.; Fiorica, C.; Giammona, G.; Cavallaro, G. Inulin derivatives obtained via enhanced microwave synthesis for nucleic acid based drug delivery. Curr. Drug Targets 2015, 16, 1650–1659.CrossRefGoogle Scholar
  19. [19]
    Mauro, N.; Campora, S.; Scialabba, C.; Adamo, G.; Licciardi, M.; Ghersi, G.; Gaetano, G. Self-organized environmentsensitive inulin–doxorubicin conjugate with a selective cytotoxic effect towards cancer cells. RSC Adv. 2015, 5, 32421–32430.CrossRefGoogle Scholar
  20. [20]
    Mandracchia, D.; Tripodo, G.; Trapani, A.; Ruggieri, S.; Annese, T.; Chlapanidas, T.; Trapani, G.; Ribatti, D. Inulin based micelles loaded with curcumin or celecoxib with effective anti-angiogenic activity. Eur. J. Pharm. Sci. 2016, 93, 141–146.CrossRefGoogle Scholar
  21. [21]
    Li, Y. P.; Xiao, K.; Zhu, W.; Deng, W. B.; Lam, K. S. Stimuli-responsive cross-linked micelles for on-demand drug delivery against cancers. Adv. Drug Deliv. Rev. 2014, 66, 58–73.CrossRefGoogle Scholar
  22. [22]
    Wu, L. L.; Zou, Y.; Deng, C.; Cheng, R.; Meng, F. H.; Zhong, Z. Y. Intracellular release of doxorubicin from corecrosslinked polypeptide micelles triggered by both pH and reduction conditions. Biomaterials 2013, 34, 5262–5272.CrossRefGoogle Scholar
  23. [23]
    Riemer, J.; Hoepken, H. H.; Czerwinska, H.; Robinson, S. R.; Dringen, R. Colorimetric ferrozine-based assay for the quantitation of iron in cultured cells. Anal. Biochem. 2004, 331, 370–375.CrossRefGoogle Scholar
  24. [24]
    Asadov, Y. G.; Alyev, Y. I.; Jafarov, K. M. X-ray diffraction study of compounds in the Ag2S-Cu2S system. Inorg. Mater. 2008, 44, 460–466.Google Scholar
  25. [25]
    Licciardi, M.; Scialabba, C.; Sardo, C.; Cavallaro, G.; Giammona, G. Amphiphilic inulin graft co-polymers as self-assembling micelles for doxorubicin delivery. J. Mater. Chem. B 2014, 2, 4262–4271.CrossRefGoogle Scholar
  26. [26]
    Li Volsi, A.; Jimenez De Aberasturi, D.; Henriksen-Lacey, M.; Giammona, G.; Licciardi, M.; Liz-Marzán, L. M. Inulin coated plasmonic gold nanoparticles as a tumor-selective tool for cancer therapy. J. Mater. Chem. B 2016, 4, 1150–1155.CrossRefGoogle Scholar
  27. [27]
    Suk, J. S.; Xu, Q. G.; Kim, N.; Hanes, J.; Ensign, L. M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 2016, 99, 28–51.CrossRefGoogle Scholar
  28. [28]
    Cavallaro, G.; Licciardi, M.; Pitarresi, G.; Giammona, G. Folate-mediated targeting of polymers as components of colloidal drug delivery systems. In Handbook of Drug Targeting and Monitoring; Andreev, B., Ed.; Nova Science Publishers Inc.: NY,2010.Google Scholar
  29. [29]
    Zwicke, G. L.; Mansoori, G. A.; Jeffery, C. J. Utilizing the folate receptor for active targeting of cancer nanotherapeutics. Nano Rev. 2012, 3, 18496–18507.CrossRefGoogle Scholar
  30. [30]
    Hilgenbrink, A. R.; Low, P. S. Folate receptor-mediated drug targeting: From therapeutics to diagnostics. J. Pharm. Sci. 2005, 94, 2135–2146.CrossRefGoogle Scholar
  31. [31]
    Lamberti, G.; Cavallaro, G.; Sardo, C.; Scialabba, C.; Licciardi, M.; Giammona, G. Smart inulin-based polycationic nanodevices for siRNA delivery. Curr. Drug Deliv. 2017, 14, 224–230.Google Scholar
  32. [32]
    Palumbo, F. S.; Fiorica, C.; Di Stefano, M.; Pitarresi, G.; Gulino, A.; Agnello, S.; Gaetano, G. In situ forming hydrogels of hyaluronic acid and inulin derivatives for cartilage regeneration. Carbohydr. Polym. 2015, 122, 408–416.CrossRefGoogle Scholar
  33. [33]
    Mandracchia, D.; Tripodo, G.; Latrofa, A.; Dorati, R. Amphiphilic inulin-D-a-tocopherol succinate (INVITE) bioconjugates for biomedical applications. Carbohydr. Polym. 2014, 103, 46–54.CrossRefGoogle Scholar
  34. [34]
    Mandracchia, D.; Denora, N.; Franco, M.; Pitarresi, G.; Giammona, G.; Trapani, G. New biodegradable hydrogels based on inulin and α,β-polyaspartylhydrazide designed for colonic drug delivery: In vitro release of glutathione and oxytocin. J. Biomater. Sci. Polym. 2011, 22, 313–328.CrossRefGoogle Scholar
  35. [35]
    Yoon, H. Y.; Saravanakumar, G.; Heo, R.; Choi, S. H.; Song, I. C.; Han, M. H.; Kim, K.; Park, J. H.; Choi, K.; Kwon, I. C. et al. Hydrotropic magnetic micelles for combined magnetic resonance imaging and cancer therapy. J. Control. Release 2012, 160, 692–698.CrossRefGoogle Scholar
  36. [36]
    Muscas, G.; Concas, G.; Cannas, C.; Musinu, A.; Ardu, A.; Orrù, F.; Fiorani, D.; Laureti, S.; Rinaldi, D.; Piccaluga, G. et al. Magnetic properties of small magnetite nanocrystals. J. Phys. Chem. C 2013, 117, 23378–23384.CrossRefGoogle Scholar
  37. [37]
    Belviso, C.; Agostinelli, E.; Belviso, S.; Cavalcante, F.; Pascucci, S.; Peddis, D.; Varvaro, G.; Fiore, S. Synthesis of magnetic zeolite at low temperature using a waste material mixture: Fly ash and red mud. Microporous Mesoporous Mater. 2015, 202, 208–216.CrossRefGoogle Scholar
  38. [38]
    Peddis, D.; Cannas, C.; Piccaluga, G.; Agostinelli, E.; Fiorani, D. Spin-glass-like freezing and enhanced magnetization in ultra-small CoFe2O4 nanoparticles. Nanotechnology 2010, 21, 125705.CrossRefGoogle Scholar
  39. [39]
    Gittleman, J. I.; Abeles, B.; Bozowski, S. Superparamagnetism and relaxation effects in granular Ni-SiO2 and Ni-Al2O3 films. Phys. Rev. B 1974, 9, 3891–3897.CrossRefGoogle Scholar
  40. [40]
    Peddis, D.; Cannas, C.; Musinu, A.; Ardu, A.; Orrù, F.; Fiorani, D.; Laureti, S.; Rinaldi, D.; Muscas, G.; Concas, G. et al. Beyond the effect of particle size: Influence of CoFe2O4 nanoparticle arrangements on magnetic properties. Chem. Mater. 2013, 25, 2005–2013.CrossRefGoogle Scholar
  41. [41]
    Peddis, D.; Rinaldi, D.; Ennas, G.; Scano, A.; Agostinelli, E.; Fiorani, D. Superparamagnetic blocking and superspin-glass freezing in ultra small δ-(Fe0.67Mn0.33)OOH particles. Phys. Chem. Chem. Phys. 2012, 14, 3162–3169CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Cinzia Scialabba
    • 1
  • Roberto Puleio
    • 2
  • Davide Peddis
    • 3
  • Gaspare Varvaro
    • 3
  • Pietro Calandra
    • 4
  • Giovanni Cassata
    • 2
  • Luca Cicero
    • 2
  • Mariano Licciardi
    • 1
    • 5
  • Gaetano Giammona
    • 1
    • 5
  1. 1.Department of Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF)University of PalermoPalermoItaly
  2. 2.Istituto Zooprofilattico Sperimentale della Sicilia “A. Mirri”PalermoItaly
  3. 3.Institute of Structure of Matter National Research Council (CNR)Monterotondo Scalo (RM)Italy
  4. 4.Istituto per lo Studio dei Materiali Nanostrutturati Consiglio Nazionale delle RicercheMonterotondo Stazione (RM)Italy
  5. 5.Mediterranean Center for Human Health Advanced Biotechnologies (CHAB), ATeNCenterUniversity of PalermoPalermoItaly

Personalised recommendations