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Engineering a pH/Glutathione-Responsive Tea Polyphenol Nanodevice as an Apoptosis/Ferroptosis-Inducing Agent
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-06-02 , DOI: 10.1021/acsabm.0c00225 Min Mu 1 , Yuelong Wang 1 , Shasha Zhao 1 , Xiaoling Li 1 , Rangrang Fan 1 , Lan Mei 1 , Min Wu 1 , Bingwen Zou 1 , Na Zhao 2 , Bo Han 2 , Gang Guo 1
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-06-02 , DOI: 10.1021/acsabm.0c00225 Min Mu 1 , Yuelong Wang 1 , Shasha Zhao 1 , Xiaoling Li 1 , Rangrang Fan 1 , Lan Mei 1 , Min Wu 1 , Bingwen Zou 1 , Na Zhao 2 , Bo Han 2 , Gang Guo 1
Affiliation
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Chemotherapy works against tumors by inducing cell apoptosis; however, evasion of apoptosis is recognized to result in resistance to anticancer therapy. Ferroptosis is an iron-dependent cell death pathway that differs from apoptosis in morphological, biochemical, and genetic levels. Combined ferroptosis and apoptosis may shed light on strategies for cancer treatment. Therefore, we have designed a nanoparticle (NP) that can simultaneously cause tumor cell apoptosis and ferroptosis. This NP is composed of epigallocatechin gallate (EGCG) and Fe3+ through a simple and green process and can be used to deliver doxorubicin hydrochloride (DOX) and iron ions to the tumor site at the same time. DOX/Fe3+/EGCG (DF) NPs display a great resolubility and long-term storage stability, and efficient DOX and Fe3+ release is realized after cellular internalization under the high level of glutathione and acidic nature in tumor. EGCG is likely to chemically reduce the released Fe3+ to Fe2+. The generated Fe3+/Fe2+ converts intracellular H2O2 to hydroxyl radicals (•OH) via the Fenton reaction. In addition, the generated •OH subsequently induces lethal ferroptosis to improve DOX-induced apoptosis. In vitro and in vivo investigations indicate that a great therapeutic effect was achieved, suggesting that the formation of the DF NP delivery system is a promising strategy to fight against tumors by an apoptosis and ferroptosis combination modality.
中文翻译：
设计一种 pH/谷胱甘肽响应型茶多酚纳米器件作为细胞凋亡/铁死亡诱导剂
化疗通过诱导细胞凋亡来对抗肿瘤；然而，人们认为逃避细胞凋亡会导致对抗癌治疗的抵抗。铁死亡是一种铁依赖性细胞死亡途径，在形态、生化和遗传水平上与细胞凋亡不同。铁死亡和细胞凋亡的结合可能会揭示癌症治疗的策略。因此，我们设计了一种可以同时引起肿瘤细胞凋亡和铁死亡的纳米颗粒（NP）。该NP由表没食子儿茶素没食子酸酯（EGCG）和Fe 3+通过简单且绿色的工艺组成，可用于将盐酸多柔比星（DOX）和铁离子同时递送至肿瘤部位。DOX/Fe 3+/EGCG (DF) NPs表现出很好的溶解性和长期储存稳定性，在肿瘤内高水平的谷胱甘肽和酸性性质下，细胞内化后实现了有效的DOX和Fe 3+释放。EGCG很可能将释放的Fe 3+化学还原为Fe 2+。生成的Fe 3+ /Fe 2+通过芬顿反应将细胞内的H 2 O 2转化为羟基自由基( • OH)。此外，生成的•OH 随后诱导致命的铁死亡以改善 DOX 诱导的细胞凋亡。体外和体内研究表明取得了很好的治疗效果，这表明 DF NP 递送系统的形成是一种通过细胞凋亡和铁死亡组合方式对抗肿瘤的有前景的策略。
更新日期：2020-07-20
中文翻译：
设计一种 pH/谷胱甘肽响应型茶多酚纳米器件作为细胞凋亡/铁死亡诱导剂
化疗通过诱导细胞凋亡来对抗肿瘤；然而，人们认为逃避细胞凋亡会导致对抗癌治疗的抵抗。铁死亡是一种铁依赖性细胞死亡途径，在形态、生化和遗传水平上与细胞凋亡不同。铁死亡和细胞凋亡的结合可能会揭示癌症治疗的策略。因此，我们设计了一种可以同时引起肿瘤细胞凋亡和铁死亡的纳米颗粒（NP）。该NP由表没食子儿茶素没食子酸酯（EGCG）和Fe 3+通过简单且绿色的工艺组成，可用于将盐酸多柔比星（DOX）和铁离子同时递送至肿瘤部位。DOX/Fe 3+/EGCG (DF) NPs表现出很好的溶解性和长期储存稳定性，在肿瘤内高水平的谷胱甘肽和酸性性质下，细胞内化后实现了有效的DOX和Fe 3+释放。EGCG很可能将释放的Fe 3+化学还原为Fe 2+。生成的Fe 3+ /Fe 2+通过芬顿反应将细胞内的H 2 O 2转化为羟基自由基( • OH)。此外，生成的•OH 随后诱导致命的铁死亡以改善 DOX 诱导的细胞凋亡。体外和体内研究表明取得了很好的治疗效果，这表明 DF NP 递送系统的形成是一种通过细胞凋亡和铁死亡组合方式对抗肿瘤的有前景的策略。
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