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首页> 外文期刊>Biomaterials Science >T cell membrane cloaking tumor microenvironmentresponsive nanoparticles with a smart 'membrane escape mechanism' for enhanced immunechemotherapy of melanoma
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T cell membrane cloaking tumor microenvironmentresponsive nanoparticles with a smart 'membrane escape mechanism' for enhanced immunechemotherapy of melanoma

机译：T细胞膜具有智能“膜逃逸机制”的肿瘤肿瘤微环境范围纳米颗粒，用于增强黑色素瘤的免疫疗法

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摘要

The application of combination immune-chemotherapy makes up for the limitation of monotherapy and achieves superior antitumor activity against cancer. However, combinational therapy is always restricted by poor tumor targeted drug delivery efficacy. Herein, novel T cell membrane cloaking tumor microenvironment- responsive nanoparticles (PBA modified T cell membrane cloaking hyaluronic acid (HA)- disulfide bond-vitamin E succinate/curcumin, shortened as RCM@T) were developed. T cell membrane cloaking not only serves as a protection shell for sufficient drug delivery but also acts as a programmed cell death-1(PD-1) "antibody" to selectively bind the PD-L1 of tumor cells. When RCM@T is intravenously administrated into the blood stream, it accumulates at tumor sites and responds to an acidic pH to achieve a "membrane escape effect" and expose the HA residues of RCM for tumor targeted drug delivery. RCM accumulates in the cytoplasm via CD44 receptor mediated endocytosis and intracellularly releases antitumor drug in the intracellular redox microenvironment for tumor chemotherapy. T cell membrane debris targets the PD-L1of tumor cells for tumor immunotherapy, which not only directly kills tumor cells, but also improves the CD8~+ T cell level and facilitates effector cytokine release. Taken together, the as-constructed RCM@T creates a new way for the rational design of a drug delivery system via the combination of stimuli-responsive drug release, chemotherapeutical agent delivery and cell membrane based immune checkpoint blockade immunotherapy.
机译：组合免疫化疗的应用弥补了单药治疗的限制，实现了抗癌的优越抗肿瘤活性。然而，组合治疗总是受到患者靶向药物递送疗效的差异差的疗法。这里，开发了新型T细胞膜的新型T细胞膜微环境 - 响应纳米颗粒（PBA改性T细胞膜粘附透明质酸（HA） - 二硫键 - 维生素E琥珀酸酯/姜黄素，缩短为RCM @ T）。 T细胞膜粘附不仅用作保护壳，用于足够的药物递送，而且还用作编程的细胞死亡-1（PD-1）“抗体”以选择性地结合肿瘤细胞的PD-L1。当RCM @ T静脉内施入血液流时，它会在肿瘤部位累积并响应酸性pH以实现“膜逃逸效应”，并暴露RCM的HA残基用于肿瘤靶向药物递送。 RCM通过CD44受体介导的内吞作用和细胞内释放抗肿瘤药物在细胞内氧化还原微环境中的肿瘤化疗中的抗肿瘤药物累积。 T细胞膜碎片靶向肿瘤免疫疗法的PD-L1OF肿瘤细胞，其不仅直接杀死肿瘤细胞，而且还改善了CD8〜+ T细胞水平并促进效应细胞因子释放。占据了AS构建的RCM @ T通过刺激响应药物释放，化学药物递送和基于细胞膜的免疫检查点阻断免疫疗法来为药物递送系统的合理设计创造了一种新的方法。

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  • 来源
    《Biomaterials Science》 |2021年第9期|共12页
  • 作者

    Xiaofang Li; Wen Zhang; Jing Lin; Hao Wu; Yucen Yao; Jiayi Zhang; Chunrong Yang;

  • 作者单位

    College Pharmacy Jiamusi University 258 Xuefu Street Jiamusi Heilongjiang 154007 China;

    College Pharmacy Jiamusi University 258 Xuefu Street Jiamusi Heilongjiang 154007 China;

    College Pharmacy Jiamusi University 258 Xuefu Street Jiamusi Heilongjiang 154007 China;

    College Pharmacy Jiamusi University 258 Xuefu Street Jiamusi Heilongjiang 154007 China;

    College Pharmacy Jiamusi University 258 Xuefu Street Jiamusi Heilongjiang 154007 China;

    College Pharmacy Jiamusi University 258 Xuefu Street Jiamusi Heilongjiang 154007 China;

    College Pharmacy Jiamusi University 258 Xuefu Street Jiamusi Heilongjiang 154007 China;

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  • 正文语种 eng
  • 中图分类 计量学;
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