Glucocorticoids delivered by inorganic-organic hybrid nanoparticles mitigate acute graft-versus-host disease and sustain graft-versus-leukemia activity
Open Access
- 1 August 2020
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 50 (8), 1220-1233
- https://doi.org/10.1002/eji.201948464
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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (1631/17‐1)
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