纳米载体
上睑下垂
表观遗传学
顺铂
基因沉默
化疗
癌症研究
生物
细胞凋亡
药理学
生物化学
药品
程序性细胞死亡
基因
遗传学
作者
Jin‐Xuan Fan,Rong‐Hui Deng,He Wang,Xinhua Liu,Xia‐Nan Wang,Renyi Qin,Xin Jin,Tiechi Lei,Di‐Wei Zheng,Panghu Zhou,Yunxia Sun,Xian‐Zheng Zhang
出处
期刊:Nano Letters
[American Chemical Society]
日期:2019-09-27
卷期号:19 (11): 8049-8058
被引量:170
标识
DOI:10.1021/acs.nanolett.9b03245
摘要
Pyroptosis is a lytic and inflammatory form of programmed cell death and could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated by the DFNA5 gene) during the caspase-3-mediated pyroptosis process is absent in most tumor cells because of the hypermethylation of DFNA5 (deafness autosomal dominant 5) gene. Here, we develop a strategy of combining decitabine (DAC) with chemotherapy nanodrugs to trigger pyroptosis of tumor cells by epigenetics, further enhancing the immunological effect of chemotherapy. DAC is pre-performed with specific tumor-bearing mice for demethylation of the DFNA5 gene in tumor cells. Subsequently, a commonly used tumor-targeting nanoliposome loaded with cisplatin (LipoDDP) is used to administrate drugs for activating the caspase-3 pathway in tumor cells and trigger pyroptosis. Experiments demonstrate that the reversal of GSDME silencing in tumor cells is achieved and facilitates the occurrence of pyroptosis. According to the anti-tumor activities, anti-metastasis results, and inhibition of recurrence, this pyroptosis-based chemotherapy strategy enhances immunological effects of chemotherapy and also provides an important insight into tumor immunotherapy.
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