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Synthesis and characterisation of iron oxide nanoparticles conjugated with epidermal growth factor receptor (EGFR) monoclonal antibody as MRI contrast agent for cancer detection

Synthesis and characterisation of iron oxide nanoparticles conjugated with epidermal growth factor receptor (EGFR) monoclonal antibody as MRI contrast agent for cancer detection

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The aim of this study is to synthesise superparamagnetic iron oxide nanoparticles conjugated with anti-epidermal growth factor receptor monoclonal antibody (ANTI-EGFR-SPION) and investigate its physicochemical characterisation and biocompatibility as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection in EGFR expressing tumour cells. These particles employed biocompatible polymers, poly(D,L-lactide-co-glycolide) (PLGA) and polyethylene glycol aldehyde (PEG-aldehyde), to increase the half-life of particles in circulation and reduce their side effects. The Fe3O4-loaded PLGA-PEG-aldehyde nanoparticles were prepared by a modified water-in-oil-in-water double emulsion method. The EGFR antibody was conjugated to the surface of SPIONs using the aldehyde-amine reaction. Synthesised conjugates (nanoprobes) were characterised using Fourier transform infrared spectrophotometry, dynamic light scattering, transmission electron microscopy images, and vibrating-sample magnetometery, and the results showed that the conjugation was successful. The mean diameter of nanoprobes was about 25 nm. These nanoprobes exhibited excellent water-solubility, stability, and biocompatibility. Meanwhile, MR susceptibility test proved that synthesised nanoprobes can be managed for negative contrast enhancement. The results of this study suggested the potential use of these nanoprobes for non-invasive molecular MRI in EGFR detection in the future.


    1. 1)
      • 40. Kumar, M.R., Bakowsky, U., Lehr, C.: ‘Preparation and characterization of cationic PLGA nanospheres as DNA carriers’, Biomaterials, 2004, 25, (10), pp. 17711777.
    2. 2)
      • 5. Tseng, S.-H., Chou, M.-Y., Chu, I.-M.: ‘Cetuximab-conjugated iron oxide nanoparticles for cancer imaging and therapy’, Int. J. Nanomed., 2015, 10, p. 3663.
    3. 3)
      • 1. Gupta, A.K., Naregalkar, R.R., Vaidya, V.D., et al: ‘Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications’, Nanomedicine (Lond.), 2007, 2, (1), pp. 2339.
    4. 4)
      • 3. Khaniabadi, P.M., Shahbazi-Gahrouei, D., Majid, A.M.S.A., et al: ‘In vitro study of SPIONs-C595 as molecular imaging probe for specific breast cancer (MCF-7) cells detection’, Iran. Biomed. J., 2017, 21, (6), p. 360.
    5. 5)
      • 37. Akbarzadeh, A., Samiei, M., Joo, S.W., et al: ‘Synthesis, characterization and in vitro studies of doxorubicin-loaded magnetic nanoparticles grafted to smart copolymers on A549 lung cancer cell line’, J. Nanobiotechnol., 2012, 10, (1), p. 46.
    6. 6)
      • 24. Varella-Garcia, M., Mitsudomi, T., Yatabe, Y., et al: ‘EGFR and HER2 genomic gain in recurrent non-small cell lung cancer after surgery: impact on outcome to treatment with gefitinib and association with EGFR and KRAS mutations in a Japanese cohort’, J. Thoracic Oncol., 2009, 4, (3), pp. 318325.
    7. 7)
      • 30. Veronese, F.M., Pasut, G.: ‘PEGylation, successful approach to drug delivery’, Drug Discov. Today, 2005, 10, (21), pp. 14511458.
    8. 8)
      • 15. Tartaj, P., del Puerto Morales, M., Veintemillas-Verdaguer, S., et al: ‘The preparation of magnetic nanoparticles for applications in biomedicine’, J. Phys. D, Appl. Phys., 2003, 36, (13), p. R182.
    9. 9)
      • 29. Na, D.H., Lee, K.C., DeLuca, P.P.: ‘PEGylation of octreotide: II. Effect of N-terminal mono-PEGylation on biological activity and pharmacokinetics’, Pharm. Res., 2005, 22, (5), pp. 743749.
    10. 10)
      • 49. Zahraei, M., Marciello, M., Lazaro-Carrillo, A., et al: ‘Versatile theranostics agents designed by coating ferrite nanoparticles with biocompatible polymers’, Nanotechnology, 2016, 27, (25), p. 255702.
    11. 11)
      • 25. Mohammadi, A., Barikani, M.: ‘Synthesis and characterization of superparamagnetic Fe3O4 nanoparticles coated with thiodiglycol’, Mater. Charact., 2014, 90, pp. 8893.
    12. 12)
      • 12. Lahaye, M.J., Engelen, S.M., Kessels, A.G., et al: ‘USPIO-enhanced MR imaging for nodal staging in patients with primary rectal cancer: predictive criteria’, Radiology, 2008, 246, (3), pp. 804811.
    13. 13)
      • 11. Heesakkers, R.A., Hövels, A.M., Jager, G.J., et al: ‘MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study’, Lancet Oncol., 2008, 9, (9), pp. 850856.
    14. 14)
      • 34. Lu, W., Zhang, Y., Tan, Y.-Z., et al: ‘Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery’, J. Control. Release, 2005, 107, (3), pp. 428448.
    15. 15)
      • 16. Nicolas, J., Mura, S., Brambilla, D., et al: ‘Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery’, Chem. Soc. Rev., 2013, 42, (3), pp. 11471235.
    16. 16)
      • 14. Danhier, F., Ansorena, E., Silva, J.M., et al: ‘PLGA-based nanoparticles: an overview of biomedical applications’, J. Control. Release, 2012, 161, (2), pp. 505522.
    17. 17)
      • 32. Yu, D.-H., Lu, Q., Xie, J., et al: ‘Peptide-conjugated biodegradable nanoparticles as a carrier to target paclitaxel to tumor neovasculature’, Biomaterials, 2010, 31, (8), pp. 22782292.
    18. 18)
      • 48. Tong, S., Hou, S., Zheng, Z., et al: ‘Coating optimization of superparamagnetic iron oxide nanoparticles for high T2 relaxivity’, Nano Lett., 2010, 10, (11), pp. 46074613.
    19. 19)
      • 19. Si, S., Li, C., Wang, X., et al: ‘Magnetic monodisperse Fe3O4 nanoparticles’, Cryst. Growth Des., 2005, 5, (2), pp. 391393.
    20. 20)
      • 41. Prabha, S., Zhou, W.-Z., Panyam, J., et al: ‘Size-dependency of nanoparticle-mediated gene transfection: studies with fractionated nanoparticles’, Int. J. Pharm., 2002, 244, (1–2), pp. 105115.
    21. 21)
      • 4. Khaniabadi, P.M., Majid, A., Asif, M., et al: ‘Breast cancer cell targeted MR molecular imaging probe: anti-MUC1 antibody-based magnetic nanoparticles’, J. Phys., Conf. Ser., 2017, 851, p. 012014.
    22. 22)
      • 27. Wassel, R.A., Grady, B., Kopke, R.D., et al: ‘Dispersion of super paramagnetic iron oxide nanoparticles in poly(D,L-lactide-co-glycolide) microparticles’, Colloids Surf. A, Physicochem. Eng. Aspects, 2007, 292, (2–3), pp. 125130.
    23. 23)
      • 23. Sadhukha, T., Wiedmann, T.S., Panyam, J.: ‘Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy’, Biomaterials, 2013, 34, (21), pp. 51635171.
    24. 24)
      • 6. Chen, H.-.L, Hsu, F.-T., Kao, Y.-C.J., et al: ‘Identification of epidermal growth factor receptor-positive glioblastoma using lipid-encapsulated targeted superparamagnetic iron oxide nanoparticles in vitro’, J. Nanobiotechnol., 2017, 15, (1), p. 86.
    25. 25)
      • 22. Scaltriti, M., Baselga, J.: ‘The epidermal growth factor receptor pathway: a model for targeted therapy’, Clin. Cancer Res., 2006, 12, (18), pp. 52685272.
    26. 26)
      • 28. Bootdee, K., Nithitanakul, M., Grady, B.P.: ‘Synthesis and encapsulation of magnetite nanoparticles in PLGA: effect of amount of PLGA on characteristics of encapsulated nanoparticles’, Polym. Bull., 2012, 69, (7), pp. 795806.
    27. 27)
      • 45. Wei, Y., Han, B., Hu, X., et al: ‘Synthesis of Fe3O4 nanoparticles and their magnetic properties’, Procedia Eng., 2012, 27, pp. 632637.
    28. 28)
      • 13. Rockall, A.G., et al: ‘Diagnostic performance of nanoparticle-enhanced magnetic resonance imaging in the diagnosis of lymph node metastases in patients with endometrial and cervical cancer’, J. Clin. Oncol., 2005.
    29. 29)
      • 26. Jeong, J.H., Lim, D.W., Han, D.K., et al: ‘Synthesis, characterization and protein adsorption behaviors of PLGA/PEG di-block co-polymer blend films’, Colloids Surf. B, Biointerfaces, 2000, 18, (3–4), pp. 371379.
    30. 30)
      • 33. Yu, M.K., Park, J., Jon, S.: ‘Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy’, Theranostics, 2012, 2, (1), p. 3.
    31. 31)
      • 31. Lee, S.-J., Jeong, J.-R., Shin, S.-C., et al: ‘Nanoparticles of magnetic ferric oxides encapsulated with poly (D,L-lactide-co-glycolide) and their applications to magnetic resonance imaging contrast agent’, J. Magn. Magn. Mater., 2004, 272, pp. 24322433.
    32. 32)
      • 9. Anzai, Y., Piccoli, C.W., Outwater, E.K., et al: ‘Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: phase III safety and efficacy study’, Radiology, 2003, 228, (3), pp. 777788.
    33. 33)
      • 21. Grandis, J.R., Sok, J.C.: ‘Signaling through the epidermal growth factor receptor during the development of malignancy’, Pharmacol. Therapeutics, 2004, 102, (1), pp. 3746.
    34. 34)
      • 35. Anabousi, S., Laue, M., Lehr, C.-M., et al: ‘Assessing transferrin modification of liposomes by atomic force microscopy and transmission electron microscopy’, Eur. J. Pharm. Biopharm., 2005, 60, (2), pp. 295303.
    35. 35)
      • 20. Mu, K., Zhang, S., Ai, T., et al: ‘Monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles for imaging of epidermal growth factor receptor-targeted cells and gliomas’, Mol. Imaging, 2015, 14, (5), pp. 112.
    36. 36)
      • 42. Gaumet, M., Vargas, A., Gurny, R., et al: ‘Nanoparticles for drug delivery: the need for precision in reporting particle size parameters’, Eur. J. Pharm. Biopharm., 2008, 69, (1), pp. 19.
    37. 37)
      • 17. Sah, H., Thoma, L.A., Desu, H.R., et al: ‘Concepts and practices used to develop functional PLGA-based nanoparticulate systems’, Int. J. Nanomed., 2013, 8, p. 747.
    38. 38)
      • 8. Varallyay, P., Nesbit, G., Muldoon, L.L., et al: ‘Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors’, Am. J. Neuroradiol., 2002, 23, (4), pp. 510519.
    39. 39)
      • 39. Abdolahi, M., Shahbazi-Gahrouei, D., Laurent, S., et al: ‘Synthesis and in vitro evaluation of MR molecular imaging probes using J591 mAb-conjugated SPIONs for specific detection of prostate cancer’, Contrast Media Mol. Imaging, 2013, 8, (2), pp. 175184.
    40. 40)
      • 10. Will, O., Purkayastha, S., Chan, C., et al: ‘Diagnostic precision of nanoparticle-enhanced MRI for lymph-node metastases: a meta-analysis’, Lancet Oncol., 2006, 7, (1), pp. 5260.
    41. 41)
      • 50. Shevtsov, M.A., Nikolaev, B.P., Yakovleva, L.Y., et al: ‘Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors’, Int. J. Nanomed., 2014, 9, p.273.
    42. 42)
      • 36. Rahimi, M., Shojaei, S., Safa, K.D., et al: ‘Biocompatible magnetic tris (2-aminoethyl) amine functionalized nanocrystalline cellulose as a novel nanocarrier for anticancer drug delivery of methotrexate’, New J. Chem., 2017, 41, (5), pp. 21602168.
    43. 43)
      • 44. Bhattacharjee, S.: ‘DLS and zeta potential – what they are and what they are not?’, J. Control. Release, 2016, 235, pp. 337351.
    44. 44)
      • 7. Liu, D., Chen, C., Hu, G., et al: ‘Specific targeting of nasopharyngeal carcinoma cell line CNE1 by C225-conjugated ultrasmall superparamagnetic iron oxide particles with magnetic resonance imaging’, Acta Biochim. Biophys. Sin., 2011, 43, (4), pp. 301306.
    45. 45)
      • 18. Wang, Z., Qiao, R., Tang, N., et al: ‘Active targeting theranostic iron oxide nanoparticles for MRI and magnetic resonance-guided focused ultrasound ablation of lung cancer’, Biomaterials, 2017, 127, pp. 2535.
    46. 46)
      • 46. El Ghandoor, H., Zidan, H., Khalil, M.M., et al: ‘Synthesis and some physical properties of magnetite (Fe3O4) nanoparticles’, Int. J. Electrochem. Sci., 2012, 7, (6), pp. 57345745.
    47. 47)
      • 43. Lu, G.W., Gao, P.: ‘Emulsions and Microemulsions for Topical and Transdermal Drug Delivery’, in Kulkarni, V.S. (ed.): ‘Handbook of Non-Invasive Drug Delivery Systems’ (Elsevier Inc., Oxford, U.K., 2010), pp. 5994.
    48. 48)
      • 47. Huang, J., Wang, L., Lin, R., et al: ‘Casein-coated iron oxide nanoparticles for high MRI contrast enhancement and efficient cell targeting’, ACS Appl. Mater. Interfaces, 2013, 5, (11), pp. 46324639.
    49. 49)
      • 38. Farshbaf, M., Salehi, R., Annabi, N., et al: ‘pH-and thermo-sensitive MTX-loaded magnetic nanocomposites: synthesis, characterization, and in vitro studies on A549 lung cancer cell and MR imaging’, Drug Dev. Ind. Pharmacy, 2018, 44, (3), pp. 452462.
    50. 50)
      • 2. Lee, H., Lee, E., Kim, D.K., et al: ‘Antibiofouling polymer-coated superparamagnetic iron oxide nanoparticles as potential magnetic resonance contrast agents for in vivo cancer imaging’, J. Am. Chem. Soc., 2006, 128, (22), pp. 73837389.

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