Prevention of acute graft-versus-host disease by magnetic nanoparticles of Fe(3)O(4) combined with cyclosporin A in murine models

OBJECTIVE: To investigate the effect of magnetic nanoparticles (MNPs) of Fe(3)O(4) combined with cyclosporin A (CsA) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in murine models. METHODS: BALB/c mice preconditioned with total-body irradiation generated aGVHD and then were followed with allo-HSCT from allogeneic C57BL/6. Recipient mice were randomly divided into five groups and then given different supportive care and followed up. The physical signs and median survival time (MST) were recorded, peripheral blood cell counts were assessed, and histological changes of the main tissues were evaluated with hematoxylin-eosin staining. Furthermore, fluorescence polarization immunoassay was used to monitor the concentration of CsA. RESULTS: The irradiated-only mice developed typical aGVHD, and the typical signs of aGVHD in the skin, liver, and intestine were observed by histopathological examination. Both CsA alone and in combination with Fe(3)O(4) MNPs significantly prolonged the MST of recipient mice compared with both the control and the Fe(3)O(4) MNPs groups. Notably, a combination of CsA with Fe(3)O(4) MNPs can elevate the peripheral white blood cells and alleviate the symptoms of GVHD and the pathological damage after allo-HSCT. In addition, the concentration of CsA was higher in plasma, heart, liver, and spleen of recipient mice with supporting care of the combination of CsA with Fe(3)O(4) MNPs than with CsA alone. CONCLUSION: Taken together, Fe(3)O(4) MNPs may be used as a carrier of immunosuppressive agents to alleviate GVHD after allo-HSCT in murine models.