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Glucocorticoids delivered by inorganic-organic hybrid nanoparticles mitigate acute graft-versus-host disease and sustain graft-versus-leukemia activity.

Authors
  • Kaiser, Tina K1
  • Li, Hu1
  • Roßmann, Laura1
  • Reichardt, Sybille D1
  • Bohnenberger, Hanibal2
  • Feldmann, Claus3
  • Reichardt, Holger M1
  • 1 Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany. , (Germany)
  • 2 Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany. , (Germany)
  • 3 Institute of Inorganic Chemistry, Karlsruhe Institute of Technology, Karlsruhe, Germany. , (Germany)
Type
Published Article
Journal
European Journal of Immunology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Aug 01, 2020
Volume
50
Issue
8
Pages
1220–1233
Identifiers
DOI: 10.1002/eji.201948464
PMID: 32133644
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Glucocorticoids (GCs) are widely used to treat acute graft-versus-host disease (aGvHD) due to their immunosuppressive activity, but they also reduce the beneficial graft-versus-leukemia (GvL) effect of the allogeneic T cells contained in the graft. Here, we tested whether aGvHD therapy could be improved by delivering GCs with the help of inorganic-organic hybrid nanoparticles (IOH-NPs) that preferentially target myeloid cells. IOH-NPs containing the GC betamethasone (BMP-NPs) efficiently reduced morbidity, mortality, and tissue damage in a totally MHC mismatched mouse model of aGvHD. Therapeutic activity was lost in mice lacking the GC receptor (GR) in myeloid cells, confirming the cell type specificity of our approach. BMP-NPs had no relevant systemic activity but suppressed cytokine and chemokine gene expression locally in the small intestine, which presumably explains their mode of action. Most importantly, BMP-NPs delayed the development of an adoptively transferred B cell lymphoma better than the free drug, although the overall incidence was unaffected. Our findings thus suggest that employing IOH-NPs could diminish the risk of relapse associated with GC therapy of aGvHD patients while still allowing to efficiently ameliorate the disease. © 2020 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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