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Cleavable, Covalently Linked, Affinity Coupling Immune Magnetic Nanoparticles for Specifically Depleting T Cells

Abstract

Hematopoietic stem cell (HSC) transplantation has become an accepted therapeutic modality for patients with hematopoietic disorders. However, transplant recipients are at high risk of a severe complication known as graft versus host disease (GvHD). To reduce the risk of GvHD, depletion of T cells in donor HSCs prior to transplantation is of vital importance. Magnetic-activated cell sorting (MACS) using immuno-magnetic nanoparticles to selectively deplete T cells presents a potential solution for HSC transplantation. In this study, we presented a complete protocol for the synthesis of immuno-magnetic nanoparticles and characterised their performance for the depletion of Jurkat T cells from cell culture and from a mixture of T cells and HSCs. First, the recombinant protein A/G, an Fc-specific antibody, and magnetic nanoparticles were covalently linked by amine groups on the surface of magnetic nanoparticles and the protein using 3-(2-pyridyldithio) propionic acid N-hydroxysuccinimide ester (SPDP). Then, the anti-Jurkat T antibodies were bound to protein A/G on magnetic nanoparticles via regio-oriented affinity binding. Approximately 85 μg of protein A/G and 25 μg of antibody were bound to 1 mg of magnetic beads. The immuno-magnetic nanoparticles were capable of depleting up to 73% of Jurkat T cells from culture medium and 72% of Jurkat T cells from the mixture. In addition, we showed that our depletion protocol was able to preserve the proliferation and differentiation characteristics of HSCs. In conclusion, our immuno-magnetic nanoparticles provide a potential solution for the depletion of T-cells prior to HSCs transplantation.

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References

  1. 1.

    M.T. De la Morena and R.A. Gatti, Hematol. Oncol. Clin. 25, 1 (2011).

    Article  Google Scholar 

  2. 2.

    R. Korngold and J. Sprent, J. Exp. Med. 148, 1687 (1978).

    CAS  Article  Google Scholar 

  3. 3.

    H. Zheng, C. Matte-Martone, H. Li, B.E. Anderson, S. Venketesan, H.S. Tan, D. Jain, J. McNiff, and W.D. Shlomchik, Blood 111, 2476 (2008).

    CAS  Article  Google Scholar 

  4. 4.

    J.F. Falkenburg, H.E. Heslop, and A.J. Barrett, Biol. Blood Marrow Transplant. 14, 136 (2008).

    Article  Google Scholar 

  5. 5.

    C.A. Keever-Taylor, S.M. Devine, R.J. Soiffer, A. Mendizabal, S. Carter, M.C. Pasquini, P.N. Hari, A. Stein, H.M. Lazarus, and C. Linker, Biol. Blood Marrow Transplant. 18, 690 (2012).

    Article  Google Scholar 

  6. 6.

    M.C. Pasquini, S. Devine, A. Mendizabal, L.R. Baden, J.R. Wingard, H.M. Lazarus, F.R. Appelbaum, C.A. Keever-Taylor, M.M. Horowitz, and S. Carter, J. Clin. Oncol. 30, 3194 (2012).

    CAS  Article  Google Scholar 

  7. 7.

    S.M. Devine, S. Carter, R.J. Soiffer, M.C. Pasquini, P.N. Hari, A. Stein, H.M. Lazarus, C. Linker, E.A. Stadtmauer, and E.P. Alyea III, Biol. Blood Marrow Transplant. 17, 1343 (2011).

    Article  Google Scholar 

  8. 8.

    M.Z. Iqbal, X. Ma, T. Chen, L.E. Zhang, W. Ren, L. Xiang, and A. Wu, J. Mater. Chem. B 3, 5172 (2015).

    CAS  Article  Google Scholar 

  9. 9.

    J.G. Croissant, Y. Fatieiev, A. Almalik, and N.M. Khashab, Adv. Healthc. Mater 7, 1700831 (2018).

    Article  Google Scholar 

  10. 10.

    H.Y. Yang, Y. Li, and D.S. Lee, Adv. Ther. 1, 1800011 (2018).

    Article  Google Scholar 

  11. 11.

    F. Ahmadpoor, S.A. Shojaosadati, H. Delavari, G. Christiansen, and R. Saber, Mater. Res. Exp. 5, 055038 (2018).

    Article  Google Scholar 

  12. 12.

    D. Yang, G. Yang, P. Yang, R. Lv, S. Gai, C. Li, F. He, and J. Lin, Adv. Funct. Mater. 27, 1700371 (2017).

    Article  Google Scholar 

  13. 13.

    J.A. Marins, T. Montagnon, H. Ezzaier, C. Hurel, O. Sandre, D. Baltrunas, K. Mazeika, A. Petrov, and P. Kuzhir, ACS Appl. Nano Mater. 1, 6760 (2018).

    CAS  Article  Google Scholar 

  14. 14.

    R. Das, J. Alonso, Z. Nemati Porshokouh, V. Kalappattil, D. Torres, M.-H. Phan, E. Garaio, J.A.N. García, J.L. Sanchez Llamazares, and H. Srikanth, J. Phys. Chem. C 120, 10086 (2016).

    CAS  Article  Google Scholar 

  15. 15.

    R. Das, N. Rinaldi-Montes, J. Alonso, Z. Amghouz, E. Garaio, J. García, P. Gorria, J. Blanco, M. Phan, and H. Srikanth, ACS Appl. Mater. Interfaces 8, 25162 (2016).

    CAS  Article  Google Scholar 

  16. 16.

    Z. Nemati, R. Das, J. Alonso, E. Clements, M. Phan, and H. Srikanth, J. Electron. Mater. 46, 3764 (2017).

    CAS  Article  Google Scholar 

  17. 17.

    Z. Nemati, J. Alonso, I. Rodrigo, R. Das, E. Garaio, J.Á. García, I.A. Orue, M.-H. Phan, and H. Srikanth, J. Phys. Chem. C 122, 2367 (2018).

    CAS  Article  Google Scholar 

  18. 18.

    T.K.H. Ta, M.-T. Trinh, N.V. Long, T.T.M. Nguyen, T.L.T. Nguyen, T.L. Thuoc, B.T. Phan, D. Mott, S. Maenosono, and H. Tran-Van, Colloids Surf. Physicochem. Eng. Asp. 504, 376 (2016).

    CAS  Article  Google Scholar 

  19. 19.

    Q. Chang and H. Tang, Molecules 19, 15768 (2014).

    Article  Google Scholar 

  20. 20.

    H. Yan, J.-C. Zhang, C.-X. You, Z.-W. Song, B.-W. Yu, and Y. Shen, Int. J. Miner. Metall. Mater. 16, 226 (2009).

    CAS  Article  Google Scholar 

  21. 21.

    D. Maity, J. Ding, and J.-M. Xue, Funct. Mater. Lett. 1, 189 (2008).

    CAS  Article  Google Scholar 

  22. 22.

    M. Khosroshahi and L. Ghazanfari, Surf. Eng. 27, 508 (2011).

    Article  Google Scholar 

  23. 23.

    A. Abou-Hassan, R. Bazzi, and V. Cabuil, Angew. Chem. Int. Ed. 48, 7180 (2009).

    CAS  Article  Google Scholar 

  24. 24.

    V. Salgueiriño-Maceira, M.A. Correa-Duarte, M. Spasova, L.M. Liz-Marzán, and M. Farle, Adv. Funct. Mater. 16, 509 (2006).

    Article  Google Scholar 

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Acknowledgments

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We thank Dr. Minh-Duy Phan for his constructive suggestions.

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Correspondence to Kieu-Hanh Thi Ta or Hieu Tran-Van.

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Huynh, KQ., Duong, D.TS., Van Tran, T. et al. Cleavable, Covalently Linked, Affinity Coupling Immune Magnetic Nanoparticles for Specifically Depleting T Cells. Journal of Elec Materi 49, 6510–6518 (2020). https://doi.org/10.1007/s11664-020-08415-0

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Keywords

  • GvHD
  • HSCs
  • MACS
  • SPDP
  • T cell isolation