Lymph Node Targeted Drug Delivery for Effective Immunomodulation to Prolong the Long-Term Survival After Heart Transplantation.

The chronic rejection responses and side effects of systematic administration of immunosuppressants are the main obstacles for heart allograft and patient survival. The development of xenotransplantation also urgently requires more efficient immune regulation strategies. Herein, we demonstrate that lymph node (LN) targeted drug delivery can realize LN specific immunomodulation with attenuated immune suppression on distant peripheral immune organs to effectively prolong the long-term survival after heart transplantation in a chronic murine heart transplantation model. A chemokine C-C motif ligand 21 (CCL21) specific aptamer for LN targeting is decorated onto the surface of the hybrid nanoparticular delivery vector composed of CaCO 3 /CaP/heparin. The targeting delivery system can dramatically enhance accumulation of the loaded immunosuppressant, FTY720, in draining lymph nodes (dLNs) for inducing powerful immune suppression. Through promoting the generation of endogenous regulatory T cells and decreasing the proportion of effector T cells in dLNs after heart transplantation, our LN targeting strategy can effectively regulate local immune responses instead of the systemic immunity, which reduces the incidence of long-term complications. This study provides an efficient strategy to improve the survival rate after organ transplantation by precise and localized immunoregulation with minimized side effects of immunosuppression. This article is protected by copyright. All rights reserved.