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PEG-Iron Oxide Core-Shell Nanoparticles: In situ Synthesis and In vitro Biocompatibility Evaluation for Potential T2-MRI Applications

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Abstract

Several colloidal nanosystems have been developed aiming biomedical applications that include investigations related to magnetic resonance imaging (MRI) procedures. In this work, a core-shell structure consisting of iron oxide nanoparticles (IONPs) nucleus grafted with polyethylene glycol (PEG)4000 was prepared and evaluated by physicochemical and magnetic characterization. The polymer was covalently immobilized over nanoparticles through a simple and rapid in situ chemical method. The resulting hybrid material was capable of inducing a relevant T2 relaxation time in an average compared to marketed MRI formulations, revealing both physical characteristics and magnetic properties adequate for MRI applications. Furthermore, the in vitro biocompatibility profile was assessed by flow cytometry technique, using healthy human cell lineage (HEK-293). The results indicated good biocompatibility profile and non-anti-proliferative properties, and therefore, IONP-PEG can be considered as a new system candidate as a T2 contrast agent for MRI applications.

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References

  1. Sudame, A., Kandasamy, G., & Maity, D. (2019). Single and dual surfactants coated hydrophilic superparamagnetic iron oxide nanoparticles for magnetic fluid hyperthermia applications. Journal of Nanoscience and Nanotechnology, 19, 3991–3999. https://doi.org/10.1166/jnn.2019.16326.

    Article  Google Scholar 

  2. Xie, J., Chen, K., Huang, J., Lee, S., Wang, J., Gao, J., Li, X., & Chen, X. (2010). PET/NIRF/MRI triple functional iron oxide nanoparticles. Biomaterials, 31, 3016–3022. https://doi.org/10.1016/j.biomaterials.2010.01.010.

    Article  Google Scholar 

  3. Kandasamy, G., & Maity, D. (2015). Recent advances in superparamagnetic iron oxide nanoparticles (SPIONs) for in vitro and in vivo cancer nanotheranostics. International Journal of Pharmaceutics, 496, 191–218. https://doi.org/10.1016/J.IJPHARM.2015.10.058.

    Article  Google Scholar 

  4. Wei, Y., Zhao, M., Yang, F., Mao, Y., Xie, H., & Zhou, Q. (2016). Iron overload by superparamagnetic iron oxide nanoparticles is a high risk factor in cirrhosis by a systems toxicology assessment. Scientific Reports, 6, 1–11. https://doi.org/10.1038/srep29110.

    Article  Google Scholar 

  5. Lawaczeck, R., Menzel, M., & Pietsch, H. (2004). Superparamagnetic iron oxide particles: contrast media for magnetic resonance imaging. Applied Organometallic Chemistry, 18(10), 506–513. https://doi.org/10.1002/aoc.753.

    Article  Google Scholar 

  6. De Montferrand, C., Hu, L., Milosevic, I., Russier, V., Bonnin, D., Motte, L., & Lalatonne, Y. (2013). Iron oxide nanoparticles with sizes, shapes and compositions resulting in different magnetization signatures as potential labels for multiparametric detection. Acta Biomaterialia, 9(4), 6150–6157. https://doi.org/10.1016/j.actbio.2012.11.025.

    Article  Google Scholar 

  7. Che Rose, L., Bear, J. C., McNaughter, P. D., et al. (2016). A SPION-eicosane protective coating for water-soluble capsules: Evidence for on-demand drug release triggered by magnetic hyperthermia. Scientific Reports, 6, 20271. https://doi.org/10.1038/srep20271.

    Article  Google Scholar 

  8. Janko, C., Zaloga, J., Pöttler, M., Dürr, S., Eberbeck, D., Tietze, R., & Alexiou, C. (2017). Strategies to optimize the biocompatibility of iron oxide nanoparticles—“SPIONs safe by design”. Journal of Magnetism and Magnetic Materials, 431, 281–284. https://doi.org/10.1016/J.JMMM.2016.09.034.

    Article  Google Scholar 

  9. Jose, G., Lu, Y.-J., Chen, H.-A., Hsu, H.-L., Hung, J.-T., Anilkumar, T. S., & Chen, J.-P. (2019). Hyaluronic acid modified bubble-generating magnetic liposomes for targeted delivery of doxorubicin. Journal of Magnetism and Magnetic Materials, 474, 355–364. https://doi.org/10.1016/j.jmmm.2018.11.019.

    Article  Google Scholar 

  10. Chervanyov, A. I., & Heinrich, G. (2007). Flory radius of polymers in a periodic field: an exact analytic theory. European Physical Journal E: Soft Matter and Biological Physics, 24, 271–276. https://doi.org/10.1140/epje/i2007-10237-9.

    Article  Google Scholar 

  11. Jaiswal, M. K., Pradhan, L., Vasavada, S., De, M., Sarma, H. D., Prakash, A., & Dravid, V. P. (2015). Magneto-thermally responsive hydrogels for bladder cancer treatment: therapeutic efficacy and in vivo biodistribution. Colloids and Surfaces. B, Biointerfaces, 136, 625–633. https://doi.org/10.1016/j.colsurfb.2015.09.058.

    Article  Google Scholar 

  12. Ishida, T., Harada, M., Wang, X. Y., Ichihara, M., Irimura, K., & Kiwada, H. (2005). Accelerated blood clearance of PEGylated liposomes following preceding liposome injection: effects of lipid dose and PEG surface-density and chain length of the first-dose liposomes. Journal of Controlled Release, 105, 305–317. https://doi.org/10.1016/j.jconrel.2005.04.003.

    Article  Google Scholar 

  13. Owens, D. E., & Peppas, N. (2006). Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. International Journal of Pharmaceutics, 307, 93–102. https://doi.org/10.1016/j.ijpharm.2005.10.010.

    Article  Google Scholar 

  14. Suk, J. S., Xu, Q., Kim, N., Hanes, J., & Ensign, L. M. (2016). PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Advanced Drug Delivery Reviews, 99, 28–51. https://doi.org/10.1016/j.addr.2015.09.012.

    Article  Google Scholar 

  15. Yang, Q., Jones, S. W., Parker, C. L., Zamboni, W. C., Bear, J. E., & Lai, S. K. (2014). Evading immune cell uptake and clearance requires PEG grafting at densities substantially exceeding the minimum for brush conformation. Molecular Pharmaceutics, 11, 1250–1258. https://doi.org/10.1021/mp400703d.

    Article  Google Scholar 

  16. Walkey, C. D., Olsen, J. B., Guo, H., Emili, A., & Chan, W. C. W. (2012). Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. Journal of the American Chemical Society, 134, 2139–2147. https://doi.org/10.1021/ja2084338.

  17. de Gennes, P. G. (1980). Conformations of polymers attached to an Interface. Macromolecules, 13, 1069–1075. https://doi.org/10.1021/ma60077a009.

    Article  Google Scholar 

  18. Yang, Q., & Lai, S. K. (2015). Anti-PEG immunity: emergence, characteristics, and unaddressed questions. Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology, 7, 655–677. https://doi.org/10.1002/wnan.1339.

    Article  Google Scholar 

  19. Lopes, T. C. M., Silva, D. F., Costa, W. C., Frézard, F., Barichello, J. M., Silva-Barcellos, N. M., Lima, W. G., & Rezende, S. A. (2018). Accelerated blood clearance (ABC) phenomenon favors the accumulation of tartar emetic in pegylated liposomes in BALB/c mice liver. Pathology Research International, 2018, 1–7. https://doi.org/10.1155/2018/9076723.

    Article  Google Scholar 

  20. Wang, L., Su, Y., Wang, X., Liang, K., Liu, M., Tang, W., Song, Y., Liu, X., & Deng, Y. (2017). Effects of complement inhibition on the ABC phenomenon in rats. Asian Journal of Pharmaceutical Sciences, 12, 250–258. https://doi.org/10.1016/J.AJPS.2016.06.004.

    Article  Google Scholar 

  21. Kang, M. K., Mao, W., & Yoo, H. S. (2018). Surface-initiated atom transfer radical polymerization of cationic corona on iron oxide nanoparticles for magnetic sorting of macrophages. Biomaterials Science, 6, 2248–2260. https://doi.org/10.1039/c8bm00418h.

    Article  Google Scholar 

  22. Wu, W., Wu, Z., Yu, T., Jiang, C., & Kim, W.-S. (2015). Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications. Science and Technology of Advanced Materials, 16, 023501. https://doi.org/10.1088/1468-6996/16/2/023501.

    Article  Google Scholar 

  23. Wu, W., Jiang, C. Z., & Roy, V. A. L. (2016). Designed synthesis and surface engineering strategies of magnetic iron oxide nanoparticles for biomedical applications. Nanoscale, 8, 19421–19474. https://doi.org/10.1039/c6nr07542h.

    Article  Google Scholar 

  24. Gates-Rector, S., & Blanton, T. (2019). The powder diffraction file: a quality materials characterization database. Powder Diffraction, 34, 352–360. https://doi.org/10.1017/s0885715619000812.

    Article  Google Scholar 

  25. Zhang, B., Tu, Z., Zhao, F., & Wang, J. (2013). Superparamagnetic iron oxide nanoparticles prepared by using an improved polyol method. Applied Surface Science, 266, 375–379. https://doi.org/10.1016/j.apsusc.2012.12.032.

    Article  Google Scholar 

  26. Ali, S., Khan, S. A., Eastoe, J., Hussaini, S. R., Morsy, M. A., & Yamani, Z. H. (2018). Synthesis, characterization, and relaxometry studies of hydrophilic and hydrophobic superparamagnetic Fe3O4 nanoparticles for oil reservoir applications. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 543, 133–143. https://doi.org/10.1016/j.colsurfa.2018.02.002.

    Article  Google Scholar 

  27. Park, J. Y., Daksha, P., Lee, G. H., Woo, S., & Chang, Y. (2008). Highly water-dispersible PEG surface modified ultra-small superparamagnetic iron oxide nanoparticles useful for target-specific biomedical applications. Nanotechnology, 19(36), 365603. https://doi.org/10.1088/0957-4484/19/36/365603.

    Article  Google Scholar 

  28. Kim, W., Suh, C. Y., Cho, S. W., Roh, K. M., Kwon, H., Song, K., & Shon, I. J. (2012). A new method for the identification and quantification of magnetite–maghemite mixture using conventional X-ray diffraction technique. Talanta, 94, 348–352. https://doi.org/10.1016/j.talanta.2012.03.001.

    Article  Google Scholar 

  29. Karimzadeh, I., Aghazadeh, M., Doroudi, T., Ganjali, M. R., & Kolivand, P. H. (2017). Superparamagnetic iron oxide (Fe3O4) nanoparticles coated with PEG/PEI for biomedical applications: a facile and scalable preparation route based on the cathodic electrochemical deposition method. Advances in Physical Chemistry, 2017, 1–7. https://doi.org/10.1155/2017/9437487.

    Article  Google Scholar 

  30. Cooper, D. H., & Mooney, N. K. (2013). Convention on biological diversity. Encyclopedia of Biodiversity, 306–319. https://doi.org/10.1016/b978-0-12-384719-5.00418-4.

  31. Sun, N., Chen, D.-X., Gu, H.-C., & Wang, X.-L. (2009). Experimental study on relaxation time of protons in water suspensions of iron-oxide nanoparticles: waiting time dependence. Journal of Magnetism and Magnetic Materials, 321, 2971–2975. https://doi.org/10.1016/j.jmmm.2009.04.073.

    Article  Google Scholar 

  32. Cho, H. R., Choi, S. H., Lee, N., Hyeon, T., Kim, H., & Moon, W. K. (2012). Macrophages homing to metastatic lymph nodes can be monitored with ultrasensitive ferromagnetic Iron-oxide nanocubes and a 1.5T clinical MR scanner. PLoS One, 7, e29575. https://doi.org/10.1371/journal.pone.0029575.

    Article  Google Scholar 

  33. Psimadas, D., Bouziotis, P., Georgoulias, P., Valotassiou, V., Tsotakos, T., & Loudos, G. (2013). Radiolabeling approaches of nanoparticles with99mTc. Contrast Media & Molecular Imaging, 8, 333–339. https://doi.org/10.1002/cmmi.1530.

    Article  Google Scholar 

  34. Cho, K., Wang, X., Nie, S., Chen, Z., & Shin, D. M. (2008). Therapeutic nanoparticles for drug delivery in cancer. Clinical Cancer Research, 14, 1310–1316. https://doi.org/10.1158/1078-0432.ccr-07-1441.

    Article  Google Scholar 

  35. Caldorera-Moore, M., Guimard, N., Shi, L., & Roy, K. (2010). Designer nanoparticles: incorporating size, shape and triggered release into nanoscale drug carriers. Expert Opinion on Drug Delivery, 7, 479–495. https://doi.org/10.1517/17425240903579971.

    Article  Google Scholar 

  36. Xu, C., Haque, F., Jasinski, D. L., Binzel, D. W., Shu, D., & Guo, P. (2018). Favorable biodistribution, specific targeting and conditional endosomal escape of RNA nanoparticles in cancer therapy. Cancer Letters, 414, 57–70. https://doi.org/10.1016/j.canlet.2017.09.043.

    Article  Google Scholar 

  37. Feng, Q., Liu, Y., Huang, J., Chen, K., Huang, J., & Xiao, K. (2018). Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings. Scientific Reports, 8, 2082. https://doi.org/10.1038/s41598-018-19628-z.

    Article  Google Scholar 

  38. Arami, H., Khandhar, A., Liggitt, D., & Krishnan, K. M. (2015). In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles. Chemical Society Reviews, 44, 8576–8607. https://doi.org/10.1039/c5cs00541h.

    Article  Google Scholar 

  39. Joseph, E., & Singhvi, G. (2019). Multifunctional nanocrystals for cancer therapy: a potential nanocarrier. In A. M. Grumezescu (Ed.), Nanomaterials for drug delivery and therapy (1st ed., pp. 91–116). Amsterdam: Elsevier. https://doi.org/10.1016/b978-0-12-816505-8.00007-2.

    Chapter  Google Scholar 

  40. Mahdavi, M., Namvar, F., Ahmad, M., & Mohamad, R. (2013). Green biosynthesis and characterization of magnetic Iron oxide (Fe3O4) nanoparticles using seaweed (Sargassum muticum) aqueous extract. Molecules, 18, 5954–5964. https://doi.org/10.3390/molecules18055954.

    Article  Google Scholar 

  41. Petcharoen, K., & Sirivat, A. (2012). Synthesis and characterization of magnetite nanoparticles via the chemical co-precipitation method. Materials Science & Engineering, B: Solid-State Materials for Advanced Technology, 177, 421–427. https://doi.org/10.1016/j.mseb.2012.01.003.

    Article  Google Scholar 

  42. Akal, Z. Ü., Alpsoy, L., & Baykal, A. (2016). Biomedical applications of SPION@APTES@PEG-folic acid@carboxylated quercetin nanodrug on various cancer cells. Applied Surface Science, 378, 572–581. https://doi.org/10.1016/j.apsusc.2016.03.217.

    Article  Google Scholar 

  43. Dai, L., Liu, Y., Wang, Z., Guo, F., Shi, D., & Zhang, B. (2014). One-pot facile synthesis of PEGylated superparamagnetic iron oxide nanoparticles for MRI contrast enhancement. Materials Science and Engineering: C, 41, 161–167. https://doi.org/10.1016/j.msec.2014.04.041.

    Article  Google Scholar 

  44. Almaki, J. H., Nasiri, R., Idris, A., Majid, F. A. A., Salouti, M., Wong, T. S., & Amini, N. (2016). Synthesis, characterization andin vitroevaluation of exquisite targeting SPIONs–PEG–HER in HER2+ human breast cancer cells. Nanotechnology, 27, 105601. https://doi.org/10.1088/0957-4484/27/10/105601.

    Article  Google Scholar 

  45. Viali, W. R., da Silva Nunes, E., dos Santos, C. C., da Silva, S. W., Aragón, F. H., Coaquira, J. A. H., & Jafelicci, M. (2013). PEGylation of SPIONs by polycondensation reactions: a new strategy to improve colloidal stability in biological media. Journal of Nanoparticle Research, 15, 1824. https://doi.org/10.1007/s11051-013-1824-x.

    Article  Google Scholar 

  46. Sabareeswaran, A., Ansar, E. B., Harikrishna, V. P. R. V., Mohanan, P. V., & Kumary, T. V. (2016). Effect of surface-modified superparamagnetic iron oxide nanoparticles (SPIONS) on mast cell infiltration: an acute in vivo study. Nanomed-Nanotechnol, 12, 1523–1533. https://doi.org/10.1016/j.nano.2016.02.018.

    Article  Google Scholar 

  47. Thapa, B., Diaz-Diestra, D., Beltran-Huarac, J., Weiner, B. R., & Morell, G. (2017). Enhanced MRI T2 relaxivity in contrast-probed anchor-free PEGylated Iron oxide nanoparticles. Nanoscale Research Letters, 12, 312. https://doi.org/10.1186/s11671-017-2084-y.

    Article  Google Scholar 

  48. Schweiger, C., Pietzonka, C., Heverhagen, J., & Kissel, T. (2011). Novel magnetic iron oxide nanoparticles coated with poly(ethylene imine)-g-poly(ethylene glycol) for potential biomedical application: synthesis, stability, cytotoxicity and MR imaging. International Journal of Pharmaceutics, 408, 130–137. https://doi.org/10.1016/j.ijpharm.2010.12.046.

    Article  Google Scholar 

  49. Park, Y. C., Smith, J. B., Pham, T., Whitaker, R. D., Sucato, C. A., Hamilton, J. A., & Wong, J. Y. (2014). Effect of PEG molecular weight on stability, T2 contrast, cytotoxicity, and cellular uptake of superparamagnetic iron oxide nanoparticles (SPIONs). Colloids and Surfaces. B, Biointerfaces, 119, 106–114. https://doi.org/10.1016/j.colsurfb.2014.04.027.

    Article  Google Scholar 

  50. Liu, D., Wu, W., Ling, J., Wen, S., Gu, N., & Zhang, X. (2011). Effective PEGylation of iron oxide nanoparticles for high performance in vivo cancer imaging. Advanced Functional Materials, 21, 1498–1504. https://doi.org/10.1002/adfm.201001658.

    Article  Google Scholar 

  51. Al Faraj, A. (2013). Preferential magnetic nanoparticle uptake by bone marrow derived macrophages sub-populations: effect of surface coating on polarization, toxicity, and in vivo MRI detection. Journal of Nanoparticle Research, 15, 1797. https://doi.org/10.1007/s11051-013-1797.

    Article  Google Scholar 

  52. Singh, A., Verma, N., & Kumar, K. (2019). Hybrid composites: a revolutionary trend in biomedical engineering. In V. Grumezescu & A. M. Grumezescu (Eds.), Materials for biomedical engineering: bioactive materials, properties, and applications (1st ed., pp. 33–46). Elsevier, Amsterdam. https://doi.org/10.1016/b978-0-12-818431-8.00002-7.

  53. Sarasini, F. (2017). Low-velocity impact behaviour of hybrid composites. In V. K. Thakur & M. K. Thakur (Eds.), Pappu A hybrid polymer composite materials: Properties and characterisation (1st ed., pp. 151–168). Elsevier, Woodhead Publishing. https://doi.org/10.1016/b978-0-08-100787-7.00007-x.

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Funding

The authors received financial support from the CNPq (405749/2016-3) and FAPEMIG (PPM-00125-18).

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  1. Laboratório de Bioengenharia, Universidade Federal de Itajubá - campus Itabira, Rua Irma Ivone Drumond, 200, Itabira, Minas Gerais, Brazil

    Karina Almeida Barcelos, Marli Luiza Tebaldi, Nádia Miriceia Leão & Daniel Cristian Ferreira Soares

  2. Programa de Pós-Graduação em Nanotecnologia Farmacêutica (PPgNANOFARMA), Universidade Federal do Rio Grande do Norte (UFRN), Rua General Gustavo Cordeiro de Faria, S/N, Natal, Rio Grande do Norte, Brazil

    Eryvaldo Socrates Tabosa do Egito

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  1. Karina Almeida Barcelos
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Barcelos, K.A., Tebaldi, M.L., do Egito, E.S.T. et al. PEG-Iron Oxide Core-Shell Nanoparticles: In situ Synthesis and In vitro Biocompatibility Evaluation for Potential T2-MRI Applications. BioNanoSci. 10, 1107–1120 (2020). https://doi.org/10.1007/s12668-020-00791-5

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