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FA-PEG decorated MOF nanoparticles as a targeted drug delivery system for controlled release of an autophagy inhibitor

机译：Fa-PEG装饰MOF纳米粒子作为靶向药物递送系统，用于自噬抑制剂的控制释放

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摘要

A zeolitic imidazolate framework (ZIF-8) with high loading capacity and pH-responsive properties, an important subclass of metal-organic frameworks (MOFs), has become a promising material for drug delivery. A multifunctional drug delivery system (DDS) was designed in this work for effective targeting delivery of chloroquine diphosphate (CQ) as an autophagy inhibitor. The ZIF-8 nanoparticles encapsulating CQ (CQ@ZIF-8 NPs) were fabricated by a simple one-pot method and were then decorated with methoxy poly(ethylene glycol)-folate (FA-PEG), a special identifier of cancer cells, to form FA-PEG/CQ@ZIF-8. The target identification of FA-PEG/CQ@ZIF-8 NPs, compared with CQ@ZIF-8 NPs, leads to an increasing number of NPs being internalized into HeLa cells, which decreases the loss of drugs and results in high cytotoxicity of CQ for cancer cells. The lower viabilities of HeLa cells (cancer cells) and higher viabilities of HEK293 cells (healthy cells) treated with FA-PEG/CQ@ZIF-8 NPs show that the special target for cancer cells results from the combinations of folic acid and folate receptors on the surface of HeLa cells. The quantitative measurements of autophagy-related proteins and the detection of autophagy flux in HeLa cells suggest that the autophagosome formation and autophagy flux are appreciably blocked after the cells are treated with FA-PEG/CQ@ZIF-8 NPs. The ZIF-8 can disintegrate only under low pH conditions, resulting in fast and full release of CQ. The pH-responsive and tumor-targeted properties of the NPs can control the drug release and enhance the efficiency of autophagy inhibition. It indicates that the FA-PEG/CQ@ZIF-8 NPs combining target identification with controlled drug release can be used as a novel model for discussing targeted cancer therapy and inhibiting the autophagy of cancer cells.
机译：具有高负载能力和pH响应性的沸石咪唑酯骨架（ZIF-8），金属有机骨架（MOF）的重要亚类，已成为药物递送的有希望的材料。在该工作中设计了一种多功能药物递送系统（DDS），以有效地靶向氯喹二磷酸（CQ）作为自噬抑制剂。通过简单的单罐方法将ZIF-8纳米颗粒包封CQ（CQ ZIF-8NPS），然后用甲氧基聚（乙二醇）装饰 - 甲酸盐（FA-PEG），癌细胞的特殊标识符，形成FA-PEG / CQ ZIF-8。与CQ ZIF-8NPS相比，FA-PEG / CQ ZIF-8NP的目标鉴定导致越来越多的NPS内化为HELA细胞，这降低了药物的丧失并导致CQ的高细胞毒性对于癌细胞。 Heara细胞（癌细胞）和HEK293细胞（健康细胞）的较低的较低的通过FA-PEG / CQ ZIF-8NPS（健康细胞）的能力显示癌细胞的特殊靶标由叶酸和叶酸受体的组合产生在HeLa细胞的表面上。与Fa-PEG / CQ ZIF-8 NPS处理后，自噬相关蛋白质的定量测量和自噬相关蛋白质的检测表明自噬体形成和自噬磁通明显阻断。 ZIF-8只能在低pH条件下崩解，导致CQ的快速和全释放。 NPS的pH-响应性和肿瘤靶向性能可以控制药物释放并提高自噬抑制的效率。它表明FA-PEG / CQ ZIF-8 NPS与受控药物释放组合的目标鉴定可以用作讨论靶向癌症治疗并抑制癌细胞的自噬的新型模型。

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  • 来源
    《Biomaterials Science》 |2018年第10期|共10页
  • 作者

    Shi Zheqi; Chen Xuerui; Zhang Li; Ding Shiping; Wang Xu; Lei Qunfang; Fang Wenjun;

  • 作者单位

    Zhejiang Univ Dept Chem Hangzhou 310027 Peoples R China;

    Zhejiang Univ Dept Chem Hangzhou 310027 Peoples R China;

    Zhejiang Univ Dept Chem Hangzhou 310027 Peoples R China;

    Zhejiang Univ Sch Med Natl Educ Base Basic Med Sci Hangzhou 310058 Zhejiang Peoples R China;

    Hangzhou Med Coll 481 Binwen Rd Hangzhou 310053 Zhejiang Peoples R China;

    Zhejiang Univ Dept Chem Hangzhou 310027 Peoples R China;

    Zhejiang Univ Dept Chem Hangzhou 310027 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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