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.