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首页> 外文期刊>Biomaterials Science >Nanoparticle ferritin-bound erastin and rapamycin: a nanodrug combining autophagy and ferroptosis for anticancer therapy
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Nanoparticle ferritin-bound erastin and rapamycin: a nanodrug combining autophagy and ferroptosis for anticancer therapy

机译：纳米粒子铁蛋白结合的eRastin和雷帕霉素：抗癌治疗的纳米抑rug和嗜酸酯组合

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摘要

Ferroptosis and autophagy are the two forms of the regulation of cell death that play important roles in cancer therapy. However, little is known about the combination of the therapeutic effects of ferroptosis and autophagy in cancer therapy. Here, in this study, we constructed a novel carrier-free nanodrug called nanoparticle ferritin-bound erastin and rapamycin (NFER). The NFER nanodrug was prepared by the emulsification technique; it exhibited an average size of 78.8 nm and zeta potential of -25.9 +/- 3.3 mV. Controllable drug encapsulation efficiency and loading ratios in NFER could be obtained. This nanodrug showed high stability in both water and PBS for several days. The release studies demonstrated that rapamycin and erastin could reach equilibrium after 24 h and 36 h, respectively; the maximum values of the released percentages of both reached beyond 30%. An in vitro study revealed that NFER showed robust ferroptosis-inducing capability by the downregulation of glutathione peroxidase-4 (GPX4) and lipid peroxidation accumulation. The autophagy process induced by rapamycin in NFER also played an important role in strengthening ferroptosis. The selective cancer cell killing ability of NFER was verified in cancer cells and normal cells. The ferroptosis-induced cytotoxicity was confirmed through several ferroptosis and autophagy inhibitors. Furthermore, the NFER nanodrug showed an improved control of tumor recurrence in the 4T1 tumor resection model. In summary, these results demonstrated that NFER exhibited excellent properties as a nanodrug, and the cell death induced by NFER was through an autophagy-associated ferroptosis pathway. This study based on protein nanodrug-induced autophagy-associated ferroptosis would provide a new insight into cancer therapy.
机译：裂解病和自噬是细胞死亡调控的两种形式，可在癌症治疗中发挥重要作用。然而，关于糖凋亡和自噬在癌症治疗中的治疗效果的组合毫无疑问。在此，在本研究中，我们构建了一种称为纳米颗粒铁蛋白结合的eRastin和雷帕霉素（NFER）的新型携带的无载体纳米树脂。通过乳化技术制备NFER纳米树脂;它的平均尺寸为78.8nm，Zeta电位为-25.9 +/- 3.3 mV。可以获得可控药物封装效率和NFR中的负载比。该纳米树脂在水和PBS中显示出高度稳定性几天。释放研究表明，雷帕霉素和成种分别在24小时和36小时后可以达到平衡;释放百分比的最大值达到超过30％。体外研究表明，NFER通过下调谷胱甘肽过氧化物酶-4（GPX4）和脂质过氧化积累的下调来显示鲁棒的硬质源诱导能力。雷帕霉素诱导的雷帕霉素诱导的自噬过程在加强硬化方面也发挥了重要作用。 nfer的选择性癌细胞杀伤能力在癌细胞和正常细胞中验证。通过几种硬化和自噬抑制剂证实了脱盐诱导的细胞毒性。此外，NFER NANODRUG显示出4T1肿瘤切除模型中的肿瘤复发的改善控制。总之，这些结果表明，NFER表现出优异的性质作为纳米树脂，并且NFER诱导的细胞死亡通过自噬相关的脱喉途径。该研究基于蛋白质纳米树脂诱导的自噬相关性硬化，对癌症治疗提供了新的洞察力。

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  • 来源
    《Biomaterials Science》 |2019年第9期|共9页
  • 作者

    Li Yaoqi; Wang Xinyu; Yan Junjie; Liu Yu; Yang Runlin; Pan Donghui; Wang Lizhen; Xu Yuping; Li Xiaotian; Yang Min;

  • 作者单位

    Zhengzhou Univ Sch Pharmaceut Sci Zhengzhou 450001 Henan Peoples R China;

    Minist Hlth Key Lab Nucl Med Jiangsu Key Lab Mol Nucl Med Jiangsu Inst Nucl Med Wuxi 214063 Jiangsu Peoples R China;

    Minist Hlth Key Lab Nucl Med Jiangsu Key Lab Mol Nucl Med Jiangsu Inst Nucl Med Wuxi 214063 Jiangsu Peoples R China;

    Minist Hlth Key Lab Nucl Med Jiangsu Key Lab Mol Nucl Med Jiangsu Inst Nucl Med Wuxi 214063 Jiangsu Peoples R China;

    Minist Hlth Key Lab Nucl Med Jiangsu Key Lab Mol Nucl Med Jiangsu Inst Nucl Med Wuxi 214063 Jiangsu Peoples R China;

    Minist Hlth Key Lab Nucl Med Jiangsu Key Lab Mol Nucl Med Jiangsu Inst Nucl Med Wuxi 214063 Jiangsu Peoples R China;

    Minist Hlth Key Lab Nucl Med Jiangsu Key Lab Mol Nucl Med Jiangsu Inst Nucl Med Wuxi 214063 Jiangsu Peoples R China;

    Minist Hlth Key Lab Nucl Med Jiangsu Key Lab Mol Nucl Med Jiangsu Inst Nucl Med Wuxi 214063 Jiangsu Peoples R China;

    Zhengzhou Univ Sch Pharmaceut Sci Zhengzhou 450001 Henan Peoples R China;

    Zhengzhou Univ Sch Pharmaceut Sci Zhengzhou 450001 Henan Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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