Immune Responsive Release of Tacrolimus to Overcome Organ Transplant Rejection. Issue 45 (25th September 2018)

• Record Type: Journal Article
• Authors: Wu, Jindao; Zheng, Zhen; Chong, Yuanyuan; Li, Xiangcheng; Pu, Liyong; Tang, Qiyun; Yang, Liu; Wang, Xuehao; Wang, Fuqiang; Liang, Gaolin
• Is Part Of: Advanced materials. Volume 30:Issue 45(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-25
• Subjects: hydrogels -- immune responsive release -- organ transplant rejection -- protein tyrosine kinase -- tacrolimus; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.201805018
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: Transplant rejection is the key problem in organ transplantation and, in clinic, immunosuppressive agents such as tacrolimus are directly administered to the recipients after surgery for T‐cell inhibition. However, direct administration of tacrolimus may bring severe side effects to the recipients. Herein, by rational design of two hydrogelators NapPhePheGluTyrOH (1 ) and Napd ‐Phed PheGluTyrOH (2 ), a facile method of immune responsive release of tacrolimus is developed from their hydrogels to overcome organ transplantation rejection. Upon incubation with protein tyrosine kinase, which is activated in T cells after organ transplantation, the tacrolimus‐encapsulating Gel1 or Gel2 is disassembled to release tacrolimus. Cell experiments show that both Gel1 and Gel2 have better inhibition effect on the activated T cells than free drug tacrolimus. Liver transplantation experiments indicate that, after 7 days of treatment of same dose tacrolimus, the recipient rats in the Gel2 group show significantly extended median survival time of 22 days while the recipients treated with conventional tacrolimus medication have a median survival time of 13 days. It is expected herein that this "smart" facile method of immune responsive release of tacrolimus can be applied to overcome organ transplantation rejection in clinic in the near future. Abstract : Upon phosphorylation by the protein tyrosine kinase from activated T cells after organ transplantation, hydrogelators in the tacrolimus‐coassembled nanofibers will be efficiently converted to their hydrophilic phosphates, resulting in the disassembly of the nanofibers and the release of tacrolimus for T‐cell inhibition.