期刊
ADVANCED MATERIALS
卷 30, 期 45, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201805018
关键词
hydrogels; immune responsive release; organ transplant rejection; protein tyrosine kinase; tacrolimus
类别
资金
- National Natural Science Foundation of China [21725505, 81821001, 81521004]
- Jiangsu Youth Medical Talents [QNRC2016580]
- Major Program of Science and technology innovation fund of Nanjing Medical University [2017NJMUCX005]
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-dPhe-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 Gel 1 or Gel 2 is disassembled to release tacrolimus. Cell experiments show that both Gel 1 and Gel 2 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 Gel 2 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.
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