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首页> 外文期刊>Biomaterials Science >Cascaded bio-responsive delivery of eNOS gene and ZNF(580) gene to collaboratively treat hindlimb ischemia via pro-angiogenesis and anti-inflammation
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Cascaded bio-responsive delivery of eNOS gene and ZNF(580) gene to collaboratively treat hindlimb ischemia via pro-angiogenesis and anti-inflammation

机译：脑基因和ZnF（580）基因的级联生物响应递送，通过促血管生成和抗炎来协作治疗Hindlimb缺血

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摘要

Gene therapy is a promising strategy for treating ischemic disease by solving the dual dilemma of ischemia and inflammation. However, its development remains limited by inefficient gene transfection. Hence, we propose a "dual genes + all-adaptive carrier" idea. We have innovatively co-delivered eNOS gene and the ZNF(580) gene encoding its transcription factor to enhance the efficiency of eNOS expression. The overexpressed ZNF(580) protein significantly promotes angiogenesis via regulating the transcription of multiple genes. This implies a potential synergistic effect of eNOS and ZNF(580) genes in anti-ischemic therapy. Additionally, we have designed an all-adaptive gene carrier with cascaded bio-responsive functions based on the characteristic bio-signals of the ischemic site (including extracellular excessive matrix metalloproteinase-2, the endo/lysosomal pH gradient and high cytoplasmic glutathione level). This carrier can sequentially overcome transfection bottlenecks and achieve high transfection. Excitingly, this cascaded bio-responsive delivery strategy remarkably enhanced blood perfusion, accelerated angiogenesis and alleviated inflammation in critical limb ischemia (CLI) mice, which was attributed to the combined effects of pro-angiogenic ZNF(580) expression and synergistically produced eNOS expression. Thereby, we believe that the co-delivery of eNOS and ZNF(580) genes assisted by a cascaded bio-responsive carrier is a powerful strategy to treat CLI.
机译：基因治疗是通过求解缺血和炎症的双重困境来治疗缺血性疾病的有希望的策略。然而，其发展仍然受到低效转染的限制。因此，我们提出了一种“双基因+全适应载体”的想法。我们具有创新的共同交付的eNOS基因和编码其转录因子的ZnF（580）基因，以提高eNOS表达的效率。过表达的ZnF（580）蛋白通过调节多种基因的转录而显着促进血管生成。这意味着eNOS和ZnF（580）基因在抗缺血治疗中的潜在协同作用。此外，我们设计了一种基于缺血部位的特征生物信号（包括细胞外过量基质金属蛋白酶-2，内孔/溶酶体pH梯度和高细胞质谷胱甘肽水平）具有级联生物响应功能的全适应基因载体。该载体可以顺序地克服转染瓶颈并实现高转染。令人兴奋的是，这种级联的生物响应递送策略显着提高了血液灌注，加速血管生成和缓解临界肢体缺血（CLI）小鼠的炎症，其归因于促血管生成ZNF（580）表达和协同产生的eNOS表达的组合作用。因此，我们认为，通过级联生物响应载体辅助的ENOS和ZNF（580）基因的共同递送是治疗CLI的强烈策略。

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  • 来源
    《Biomaterials Science》 |2020年第23期|共16页
  • 作者

    Wang Xiaoyu; Su Bin; Gao Bin; Zhou Jiaying; Ren Xiang-kui; Guo Jintang; Xia Shihai; Zhang Wencheng; Feng Yakai;

  • 作者单位

    Tianjin Univ Sch Chem Engn &

    Technol Yaguan Rd 135 Tianjin 300350 Peoples R China;

    Chinese Peoples Armed Police Force Dept Clin Res Characterist Med Ctr Chenglin Rd 220 Tianjin 300162 Peoples R China;

    Tianjin Univ Sch Chem Engn &

    Technol Yaguan Rd 135 Tianjin 300350 Peoples R China;

    Tianjin Univ Sch Chem Engn &

    Technol Yaguan Rd 135 Tianjin 300350 Peoples R China;

    Tianjin Univ Sch Chem Engn &

    Technol Yaguan Rd 135 Tianjin 300350 Peoples R China;

    Tianjin Univ Sch Chem Engn &

    Technol Yaguan Rd 135 Tianjin 300350 Peoples R China;

    Logist Univ Peoples Armed Police Force Dept Hepatopancreatobiliary &

    Splen Med Affiliated Hosp 220 Chenglin Rd Tianjin 300162 Peoples R China;

    Logist Univ Peoples Armed Police Force Dept Physiol &

    Pathophysiol 220 Chenglin Rd Tianjin 300162 Peoples R China;

    Tianjin Univ Sch Chem Engn &

    Technol Yaguan Rd 135 Tianjin 300350 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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