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首页> 外文期刊>Advanced Functional Materials >Selective Degradation of PD-L1 in Cancer Cells by Enzyme-Instructed Self-Assembly
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Selective Degradation of PD-L1 in Cancer Cells by Enzyme-Instructed Self-Assembly

机译：酶指示自组装选择性降解癌细胞中的PD-L1

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摘要

Here, a novel strategy to selectively degrade membrane proteins of programmed cell death-ligand 1 (PD-L1) in cancer cells is reported. 4T1 cells show high levels of extracellular alkaline phosphatase (ALP) and membrane proteins of PD-L1. Therefore, peptide derivatives capable of responding to ALP and binding to PD-L1 are designed. Enzyme-instructed self-assembly (EISA) by ALP and surface-induced self-assembly by PD-L1 of Comp. 3 leads to the selective formation of nanomaterials around PD-L1 on the cell membrane, which is similar to attaching a hydrophobic label to the surface of PD-L1 to simulate its partial denaturation state. When taken up by cells, PD-L1 could be further degraded by the proteasome pathway in the cytoplasm. This process does not occur in the normal cell line, LO2 cells, which express relatively low levels of ALP. In addition to concentration and time dependence, the selective knock-out of PD-L1 by the strategy is reversible by simply removing Comp. 3. In vivo studies reveal that Comp. 3 inhibits tumor growth in a tumor-bearing mouse model. The study offers a novel platform for the precise degradation of membrane proteins using EISA, which might ultimately lead to the development of novel nanomedicines to treat diseases.
机译：这里，报道了一种新的策略，以在癌细胞中选择性降解编程细胞死亡配体1（PD-L1）的膜蛋白。 4T1细胞显示PD-L1的高水平细胞外碱性磷酸酶（ALP）和膜蛋白。因此，设计了能够应对ALP并结合PD-L1的肽衍生物。通过PD-L1通过ALP和表面诱导的自组装通过PD-L1进行酶指示自组装（EISA）。 3导致在细胞膜上的PD-L1周围的纳米材料的选择性形成，其类似于将疏水标记附着到PD-L1的表面以模拟其部分变性状态。当通过细胞占用时，PD-L1可以通过细胞质中的蛋白酶体途径进一步降解。该方法不会发生在正常细胞系LO2细胞中，其表达相对较低水平的ALP。除了浓度和时间依赖之外，通过简单地去除Comp，策略的选择性敲除PD-L1的选择性敲除。 3.体内研究表明Comp。 3抑制肿瘤小鼠模型中的肿瘤生长。该研究提供了一种新颖的平台，用于使用EISA的膜蛋白的精确降解，这可能最终导致新型纳米胺的发展治疗疾病。

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  • 来源
    《Advanced Functional Materials》 |2021年第45期|2102505.1-2102505.11|共11页
  • 作者

    Wang Yuhan; Li Xinxin; Zheng Debin; Chen Yumiao; Zhang Zhenghao; Yang Zhimou;

  • 作者单位

    Nankai Univ Collaborat Innovat Ctr Chem Sci & Engn State Key Lab Med Chem Biol Minist Educ Key Lab Bioact Mat Coll Life Sci Tianjin 300071 Peoples R China|Nankai Univ Natl Inst Funct Mat Tianjin 300071 Peoples R China;

    Nankai Univ Collaborat Innovat Ctr Chem Sci & Engn State Key Lab Med Chem Biol Minist Educ Key Lab Bioact Mat Coll Life Sci Tianjin 300071 Peoples R China|Nankai Univ Natl Inst Funct Mat Tianjin 300071 Peoples R China;

    Nankai Univ Collaborat Innovat Ctr Chem Sci & Engn State Key Lab Med Chem Biol Minist Educ Key Lab Bioact Mat Coll Life Sci Tianjin 300071 Peoples R China|Nankai Univ Natl Inst Funct Mat Tianjin 300071 Peoples R China;

    Nankai Univ Collaborat Innovat Ctr Chem Sci & Engn State Key Lab Med Chem Biol Minist Educ Key Lab Bioact Mat Coll Life Sci Tianjin 300071 Peoples R China|Nankai Univ Natl Inst Funct Mat Tianjin 300071 Peoples R China;

    Nankai Univ Collaborat Innovat Ctr Chem Sci & Engn State Key Lab Med Chem Biol Minist Educ Key Lab Bioact Mat Coll Life Sci Tianjin 300071 Peoples R China|Nankai Univ Natl Inst Funct Mat Tianjin 300071 Peoples R China;

    Nankai Univ Collaborat Innovat Ctr Chem Sci & Engn State Key Lab Med Chem Biol Minist Educ Key Lab Bioact Mat Coll Life Sci Tianjin 300071 Peoples R China|Nankai Univ Natl Inst Funct Mat Tianjin 300071 Peoples R China;

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  • 正文语种 eng
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  • 关键词

    antitumor; PD-L1; peptide; protein degradation; self-assembly;

    机译：抗肿瘤;PD-L1;肽;蛋白质退化;自组装;

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