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Nano Lett ; 19(11): 8049-8058, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31558023


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.

Adv Mater ; 31(16): e1808278, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803049


Synthetic biology based on bacteria has been displayed in antitumor therapy and shown good performance. In this study, an engineered bacterium Escherichia coli MG1655 is designed with NDH-2 enzyme (respiratory chain enzyme II) overexpression (Ec-pE), which can colonize in tumor regions and increase localized H2 O2 generation. Following from this, magnetic Fe3 O4 nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton-like reaction, which converts H2 O2 to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton-like reaction occurs with sustainably synthesized H2 O2 produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic •OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self-supplied therapeutic Fenton-like reaction without additional H2 O2 provision.

Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/metabolismo , Neoplasias/terapia , Animais , Apoptose , Reatores Biológicos , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Nanopartículas de Magnetita/química , Camundongos Endogâmicos BALB C , Oxirredução , Espécies Reativas de Oxigênio/metabolismo