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首页> 外文期刊>Biomaterials Science >Poly-gamma-glutamic acid derived nanopolyplexes for up-regulation of gamma-glutamyl transpeptidase to augment tumor active targeting and enhance synergistic antitumor therapy by regulating intracellular redox homeostasis
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Poly-gamma-glutamic acid derived nanopolyplexes for up-regulation of gamma-glutamyl transpeptidase to augment tumor active targeting and enhance synergistic antitumor therapy by regulating intracellular redox homeostasis

机译：多γ-谷氨酸衍生的纳米多单分布用于上调γ-谷氨酸酮酸酶，通过调节细胞内氧化还原稳态增强肿瘤活性靶向并增强协同抗肿瘤疗法

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摘要

The active targeting strategy has achieved inspiring progress for drug accumulation in tumor therapy; however, the insufficient expression level of many potential receptors poses challenges for drug delivery. Poly-gamma-glutamic acid (gamma-pGluA), a naturally occurring anionic biopolymer, showed high affinity with tumor-associated gamma-glutamyl transpeptidase (GGT), which localized on the cell surface and exhibited intracellular redox homeostasis-dependent expression pattern; thus, GGT was utilized for mediating endocytosis of nanoparticles. Herein, GGT-targeting nanopolyplexes (gamma-pGluA-CSO@Fe3+, PCFN) consisting of cationic chitosan and GGT-targeting gamma-pGluA blended with iron ion were constructed to load reactive oxygen species-induced menadione (MA) and doxorubicin, which were utilized to investigate the mechanism of GGT up-regulation. Briefly, the pretreated PCFN/MA induced an intracellular oxidative stress environment, which facilitated adjusted up-regulated GGT expression and boosted tumor targeting. Subsequently, the destroyed redox homeostasis sensitized tumors for synergistic therapy. The innovative strategy of augmenting active targeting by disturbing intracellular redox homeostasis offers insight for the application of gamma-pGluA-derived nanopolyplexes.
机译：积极的目标战略取得了鼓舞人心的肿瘤治疗中药物积累的进展;然而，许多潜在受体的表达水平不足会给药物递送带来挑战。多γ-谷氨酸（Gamma-PGlua）是一种天然存在的阴离子生物聚合物，与肿瘤相关的γ-谷氨酸缩肽酶（GGT）具有高亲和力，其局限于细胞表面并显示出细胞内氧化还原稳态依赖表达模式;因此，GGT用于介导纳米颗粒的内吞作用。在此，由阳离子壳聚糖和GGT靶向γ-pGlua组成的GGT靶向纳米多单分布（Gamma-pGlua-CSO @ Fe3 +，PCFn）构建与铁离子混合的Gamma-PGlua组成，以载有反应性氧物种诱导的植物和多柔比星。利用来研究GGT上调的机制。简而言之，预处理的PCFN / MA诱导细胞内氧化应激环境，其促进调节的上调的GGT表达和提升肿瘤靶向。随后，被摧毁的氧化还原稳态致敏肿瘤用于协同疗法。通过扰乱细胞内氧化还原稳态增强活性靶向的创新策略为应用γ-pGlua衍生的纳米多元分布提供了洞察力。

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  • 来源
    《Biomaterials Science》 |2020年第21期|共14页
  • 作者

    Yu Fangying; Zhu Yun; Liu Yupeng; Qiu Guoxi; Shang Xuwei; Meng Tingting; Yuan Hong; Hu Fuqiang;

  • 作者单位

    Zhejiang Univ Coll Pharmaceut Sci 866 Yuhangtang Rd Hangzhou 310058 Peoples R China;

    Nanjing Univ Sch Med Dept Pharm Nanjing Drum Tower Hosp Affiliated Hosp Nanjing 210008 Jiangsu Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci 866 Yuhangtang Rd Hangzhou 310058 Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci 866 Yuhangtang Rd Hangzhou 310058 Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci 866 Yuhangtang Rd Hangzhou 310058 Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci 866 Yuhangtang Rd Hangzhou 310058 Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci 866 Yuhangtang Rd Hangzhou 310058 Peoples R China;

    Zhejiang Univ Coll Pharmaceut Sci 866 Yuhangtang Rd Hangzhou 310058 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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