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Externally Controlled Cellular Transport of Magnetic Iron Oxide Particles with Polysaccharide Surface Coatings

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Abstract

Recently, due to their promising applications in biomedicine, magnetic iron oxide nanoparticles (MPs) have become one of the research hotspots in the nanomedicine field. Since various synthetic modifications have been widely applied to these nanoparticles for better targeting behaviors, it is meaningful to apply the optimal magnetic field condition for each case. This will enable creating a safe and efficient drug targeting using different types of MPs. In the present study, we aimed to find out any changes of transepithelial transport of polysaccharide-coated MPs by applying the continuous or the pulsatile magnetic field condition. Our results with heparin-functionalized MPs indicate that the particle concentrations and the external magnetic field could influence the transepithelial permeability of the particles. In the presence of a continuously applied magnetic density, heparin-MPs at high concentrations, by forming magnetically-induced aggregation of particles over the cell surface layer, showed a lower cellular transport than those at low concentrations. Furthermore, the results from the quantitative chemical assays and imaging analyses showed that transepithelial transport of heparin-MPs (negatively charged) under the pulsatile magnetic field was higher than that under the continuous magnetic field (CP), whereas the starch-MPs (neutrally charged) showed a small difference in transepithelial transport or cell retention between pulsatile vs. continuous magnetic field conditions. Taken together, our results suggest that the external magnetic field should be differentially applied to control the cellular drug transport depending on the physicochemical properties of the surface chemistry of magnetic particles.

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References

  1. Chomoucka, J., Drbohlavova, J., Huska, D., Adam, V., Kizek, R., & Hubalek, J. (2010). Magnetic nanoparticles and targeted drug delivering. Pharmacological Research, 62, 144–149.

    Article  CAS  PubMed  Google Scholar 

  2. Cardoso, V. F., Francesko, A., Ribeiro, C., Banobre-Lopez, M., Martins, P., & Lanceros-Mendez, S. (2018). Advances in Magnetic Nanoparticles for Biomedical Applications. Advanced healthcare materials, 7, 1700845.

    Article  CAS  Google Scholar 

  3. Kumar, C. S., & Mohammad, F. (2011). Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. Advanced Drug Delivery Reviews, 63, 789–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rumenapp, C., Gleich, B., & Haase, A. (2012). Magnetic nanoparticles in magnetic resonance imaging and diagnostics. Pharmaceutical Research, 29, 1165–1179.

    Article  CAS  PubMed  Google Scholar 

  5. Gobbo, O. L., Sjaastad, K., Radomski, M. W., Volkov, Y., & Prina-Mello, A. (2015). Magnetic nanoparticles in cancer theranostics. Theranostics, 5, 1249–1263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. McBain, S. C., Yiu, H. H., & Dobson, J. (2008). Magnetic nanoparticles for gene and drug delivery. International Journal of Nanomedicine, 3, 169–180.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Miao, L., Liu, C., Ge, J., Yang, W., Liu, J., Sun, W., et al. (2014). Antitumor effect of TRAIL on oral squamous cell carcinoma using magnetic nanoparticle-mediated gene expression. Cell Biochemistry and Biophysics, 69, 663–672.

    Article  CAS  PubMed  Google Scholar 

  8. Reddy, L. H., Arias, J. L., Nicolas, J., & Couvreur, P. (2012). Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chemical Reviews, 112, 5818–5878.

    Article  CAS  PubMed  Google Scholar 

  9. Laurent, S., Saei, A. A., Behzadi, S., Panahifar, A., & Mahmoudi, M. (2014). Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges. Expert Opinion on Drug Delivery, 11, 1449–1470.

    Article  CAS  PubMed  Google Scholar 

  10. Lu, A. H., Salabas, E. L., & Schuth, F. (2007). Magnetic nanoparticles: synthesis, protection, functionalization, and application. Angewandte Chemie, 46, 1222–1244.

    Article  CAS  PubMed  Google Scholar 

  11. Branquinho, L. C., Carriao, M. S., Costa, A. S., Zufelato, N., Sousa, M. H., Miotto, R., et al. (2013). Effect of magnetic dipolar interactions on nanoparticle heating efficiency: implications for cancer hyperthermia. Scientific Reports, 3, 2887.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Gupta, A. K., Naregalkar, R. R., Vaidya, V. D., & Gupta, M. (2007). Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications. Nanomedicine, 2, 23–39.

    Article  CAS  PubMed  Google Scholar 

  13. Easo, S. L., & Mohanan, P. V. (2013). Dextran stabilized iron oxide nanoparticles: synthesis, characterization and in vitro studies. Carbohydrate Polymers, 92, 726–732.

    Article  CAS  PubMed  Google Scholar 

  14. Hubatsch, I., Ragnarsson, E. G., & Artursson, P. (2007). Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nature Protocols, 2, 2111–2119.

    Article  CAS  PubMed  Google Scholar 

  15. Volpe, D. A. (2011). Drug-permeability and transporter assays in Caco-2 and MDCK cell lines. Future Medicinal Chemistry, 3, 2063–2077.

    Article  CAS  PubMed  Google Scholar 

  16. Beddoes, C. M., Case, C. P., & Briscoe, W. H. (2015). Understanding nanoparticle cellular entry: A physicochemical perspective. Advances in Colloid and Interface Science, 218, 48–68.

    Article  CAS  PubMed  Google Scholar 

  17. Min, K. A., Yu, F., Yang, V. C., Zhang, X., & Rosania, G. R. (2010). Transcellular transport of heparin-coated magnetic iron oxide nanoparticles (Hep-MION) under the influence of an applied magnetic field. Pharmaceutics, 2, 119–135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Min, K. A., Shin, M. C., Yu, F., Yang, M., David, A. E., Yang, V. C., et al. (2013). Pulsed magnetic field improves the transport of iron oxide nanoparticles through cell barriers. ACS Nano, 7, 2161–2171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Riemer, J., Hoepken, H. H., Czerwinska, H., Robinson, S. R., & Dringen, R. (2004). Colorimetric ferrozine-based assay for the quantitation of iron in cultured cells. Analytical Biochemistry, 331, 370–375.

    Article  CAS  PubMed  Google Scholar 

  20. Arbab, A. S., Bashaw, L. A., Miller, B. R., Jordan, E. K., Lewis, B. K., Kalish, H., et al. (2003). Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. Radiology, 229, 838–846.

    Article  PubMed  Google Scholar 

  21. Min, K. A., Rosania, G. R., & Shin, M. C. (2016). Human Airway primary epithelial cells show distinct architectures on Membrane supports under different culture conditions. Cell Biochemistry and Biophysics, 74, 191–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Konsoula, R., & Barile, F. A. (2005). Correlation of in vitro cytotoxicity with paracellular permeability in Caco-2 cells. Toxicology In vitro, 19, 675–684.

    CAS  Google Scholar 

  23. Lacombe, O., Woodley, J., Solleux, C., Delbos, J. M., Boursier-Neyret, C., & Houin, G. (2004). Localisation of drug permeability along the rat small intestine, using markers of the paracellular, transcellular and some transporter routes. European Journal of Pharmaceutical Sciences, 23, 385–391.

    Article  CAS  PubMed  Google Scholar 

  24. Chertok, B., Moffat, B. A., David, A. E., Yu, F., Bergemann, C., Ross, B. D., et al. (2008). Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials, 29, 487–496.

    Article  CAS  PubMed  Google Scholar 

  25. Cole, A. J., David, A. E., Wang, J., Galban, C. J., Hill, H. L., & Yang, V. C. (2011). Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting. Biomaterials, 32, 2183–2193.

    Article  CAS  PubMed  Google Scholar 

  26. Laurent, S., Forge, D., Port, M., Roch, A., Robic, C., Vander Elst, L., et al. (2008). Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chemical Reviews, 108, 2064–2110.

    Article  CAS  PubMed  Google Scholar 

  27. Neuberger, T., Schöpf, B., Hofmann, H., Hofmann, M., & Von Rechenberg, B. (2005). Superparamagnetic nanoparticles for biomedical applications: possibilities and limitations of a new drug delivery system. Journal of Magnetism and Magnetic Materials, 293, 483–496.

    Article  CAS  Google Scholar 

  28. Nel, A. E., Madler, L., Velegol, D., Xia, T., Hoek, E. M., Somasundaran, P. et al. (2009). Understanding biophysicochemical interactions at the nano-bio interface. Nature Materials, 8, 543–557.

    Article  CAS  PubMed  Google Scholar 

  29. Limbach, L. K., Li, Y., Grass, R. N., Brunner, T. J., Hintermann, M. A., Muller, M., et al. (2005). Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration, and diffusion at low concentrations. Environmental Science & Technology, 39, 9370–9376.

    Article  CAS  Google Scholar 

  30. Corchero, J. L., & Villaverde, A. (2009). Biomedical applications of distally controlled magnetic nanoparticles. Trends in Biotechnology, 27, 468–476.

    Article  CAS  PubMed  Google Scholar 

  31. Polyak, B., & Friedman, G. (2009). Magnetic targeting for site-specific drug delivery: applications and clinical potential. Expert Opinion on Drug Delivery, 6, 53–70.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the 2016 Inje University research grant. We thank Anjila Maharjan for the technical support.

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Authors and Affiliations

  1. College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gyeongnam, Gimhae, 621-749, Republic of Korea

    Kwan Hyung Cho & Kyoung Ah Min

  2. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Gyeongnam, Jinju, 660-701, Republic of Korea

    Meong Cheol Shin

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  1. Kwan Hyung Cho
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Correspondence to Kyoung Ah Min.

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Cho, K.H., Shin, M.C. & Min, K.A. Externally Controlled Cellular Transport of Magnetic Iron Oxide Particles with Polysaccharide Surface Coatings. Cell Biochem Biophys 77, 213–225 (2019). https://doi.org/10.1007/s12013-019-00874-5

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