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

Bibliographische Detailangaben
Veröffentlicht in:	Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 16 vom: 14. Apr., Seite e2207227
1. Verfasser:	Che, Yan-Jia (VerfasserIn)
Weitere Verfasser:	Ren, Xiao-He, Wang, Zhi-Wei, Wu, Qi, Xing, Kai, Zhang, Min, Xu, Chang, Han, Di, Yuan, Shun, Zheng, Si-Hao, Chen, Yuan-Yang, Liao, Xin-Ru, Shi, Feng, Zhong, Xiao-Han, Cai, Xin, Cheng, Si-Xue
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2023
Zugriff auf das übergeordnete Werk:	Advanced materials (Deerfield Beach, Fla.)
Schlagworte:	Journal Article aptamers heart transplantation hybrid nanoparticles immune regulation lymph-node-targeted delivery Immunosuppressive Agents Fingolimod Hydrochloride G926EC510T

Beschreibung
Zusammenfassung:	© 2022 Wiley-VCH GmbH. The chronic rejection responses and side effects of the systematic administration of immunosuppressants are the main obstacles to heart allograft and patient survival. The development of xenotransplantation also urgently requires more efficient immune regulation strategies. Herein, it is demonstrated that lymph-node (LN)-targeted drug delivery can realize LN-specific immunomodulation with attenuated immune suppression on distant peripheral immune organs to effectively prolong 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 mainly composed of CaCO3 /CaP/heparin. The targeting delivery system can dramatically enhance accumulation of the loaded immunosuppressant, fingolimod hydrochloride (FTY720), in draining lymph nodes (dLNs) for inducing powerful immune suppression. By promoting the generation of endogenous regulatory T cells (Tregs ) and decreasing the proportion of effector T cells (Teffs ) in dLNs after heart transplantation, the LN-targeting strategy can effectively regulate local immune responses instead of 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
Beschreibung:	Date Completed 21.04.2023 Date Revised 21.04.2023 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-4095
DOI:	10.1002/adma.202207227