KIT | KIT-Bibliothek | Impressum | Datenschutz

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

Kaiser, Tina K.; Li, Hu; Roßmann, Laura; Reichardt, Sybille D.; Bohnenberger, Hanibal; Feldmann, Claus; Reichardt, Holger M.

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.

Open Access Logo

Verlagsausgabe §
DOI: 10.5445/IR/1000118078
Veröffentlicht am 08.07.2020
DOI: 10.1002/eji.201948464
Zitationen: 1
Web of Science
Zitationen: 1
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Anorganische Chemie (AOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 0014-2980, 1521-4141
KITopen-ID: 1000118078
Erschienen in European journal of immunology
Verlag Wiley-VCH Verlag
Vorab online veröffentlicht am 04.03.2020
Nachgewiesen in Scopus
Web of Science
KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft
KITopen Landing Page