期刊
ACS NANO
卷 12, 期 10, 页码 9966-9973出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b04143
关键词
hepatic fibrosis; tandem; self-assembly; slow release; dexamethasone
类别
资金
- Ministry of Science and Technology of China [2016YFA0400904, 2017YFA0205600]
- National Natural Science Foundation of China [21725505, 81821001, 21675145, 81430034, 91542123]
Many chronic liver diseases will advance to hepatic fibrosis and, if without timely intervention, liver cirrhosis or even hepatocellular carcinoma. Anti-inflammation could be a standard therapeutic strategy for hepatic fibrosis treatment, but a smart strategy of hepatic fibrosis-targeted, either self-assembly or slow release of an anti-inflammation drug (e.g., dexamethasone, Dex), has not been reported. Herein, we rationally designed a hydrogelator precursor Nap-Phe-Phe-Lys(Dex)-Tyr(H2PO3)-OH (1-Dex-P) and proposed a tandem enzymatic strategy of self-assembly and slow release of Dex, with which the precursor exhibited much stronger antihepatic fibrosis effect than Dex both in vitro and in vivo. Enzymatic and cell experiments validated that 1-Dex-P was first dephosphorylated by alkaline phosphatase to yield Nap-Phe-Phe-Lys(Dex)-Tyr-OH (1-Dex), which self-assembled into nanofiber 1-Dex. The nanofiber was then hydrolyzed by esterase to transform into nanofiber 1, accompanied by slow release of Dex. We anticipate that our smart tandem enzymatic strategy could be widely employed to design more sophisticated drug delivery systems to achieve enhanced therapeutic efficacy than free drugs in the future.
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