Abstract: The prevention and the treatment of graft-versus-host disease (GVHD) remains a barrier to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Tolerogenic dendritic cells (TDCs) have become a hotspot in GVHD prevention despite the poor induction efficiency. Herein, we designed a novel size-dependent platform of graphene oxide (GO) nanosheets for neuropeptide delivery for the purpose of TDC generation. GO with a lateral sizeÓ╝×1 µm (L-GO) showed strong affinities to DC membrane, which effectively promoted the recognition between neuropeptide, urocortin (UCN) and its receptor CRHR2 and in turn benefited TDC generation through PKA C/CREB phosphorylation. Simultaneously, L-GO also elevated the expression of CCR7 and enhanced the migration ability of TDCs by mediating cytoskeleton reorganization. In vivo experiments offered direct evidence that TDCs inducted by [email protected] exhibited efficient migration to lymph nodes, abundant generation of Treg, a significant decrease of proinflammatory cytokines and in turn excellent efficiency in GVHD relief. In the current study, we proposed an innovative GO nanosheets based cytomembrane-targeted platform for neuropeptide delivery and subsequent TDC generation. In the meantime, the promoted mobility of TDC pulsed by GOs ensured the high homing efficiency to secondary lymph nodes, attributing to GVHD treatment in vivo. Thus, such work provided a promising strategy that might be applicable more broadly to delivery systems for receptor-mediated drugs, and could meet the changing demand of nanotechnology-based immunotherapy.

Journal Link: 10.21203/rs.3.rs-1148600/v1 Journal Link: Publisher Website Journal Link: Download PDF Journal Link: Google Scholar