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.

中文翻译：

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无机-有机杂化纳米颗粒释放的糖皮质激素减轻急性移植物抗宿主病并维持移植物抗白血病活性

糖皮质激素（GCs）由于其免疫抑制活性而被广泛用于治疗急性移植物抗宿主病（aGvHD），但它们也降低了移植物中所含同种异体T细胞的有益移植物抗白血病（GvL）作用。在这里，我们测试了通过优先靶向髓样细胞的无机-有机杂化纳米颗粒（IOH-NPs）递送GC是否可以改善aGvHD治疗。在完全MHC失配的aGvHD小鼠模型中，含有GC倍他米松（BMP-NP）的IOH-NP有效降低了发病率，死亡率和组织损伤。在缺乏髓样细胞中GC受体（GR）的小鼠中失去了治疗活性，这证实了我们方法的细胞类型特异性。BMP-NPs没有相关的全身活性，但是在小肠中局部抑制了细胞因子和趋化因子基因的表达，大概解释了他们的行动方式。最重要的是，尽管总发生率没有受到影响，但BMP-NPs延迟过继转移的B细胞淋巴瘤的发展要好于游离药物。因此，我们的发现表明，使用IOH-NPs可以降低与aGvHD患者的GC治疗相关的复发风险，同时仍然可以有效改善疾病。