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Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy
Nature Communications ( IF 14.7 ) Pub Date : 2019-01-16 , DOI: 10.1038/s41467-018-08234-2
Qing Wu , Zhigang He , Xia Wang , Qi Zhang , Qingcong Wei , Sunqiang Ma , Cheng Ma , Jiyu Li , Qigang Wang

As the first line of innate immune cells to migrate towards tumour tissue, neutrophils, can immediately kill abnormal cells and activate long-term specific adaptive immune responses. Therefore, the enzymes mediated elevation of reactive oxygen species (ROS) bioinspired by neutrophils can be a promising strategy in cancer immunotherapy. Here, we design a core-shell supramolecular hybrid nanogel via the surface phosphatase triggered self-assembly of oligopeptides around iron oxide nanoparticles to simulate productive neutrophil lysosomes. The cascade reaction of superoxide dismutase (SOD) and chloroperoxidase (CPO) within the bioinspired nanogel can convert ROS in tumour tissue to hypochlorous acid (HOCl) and the subsequent singlet oxygen (1O2) species. Studies on both cells and animals demonstrate successful 1O2-mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation.

中文翻译:

自组装杂交纳米凝胶中的级联酶模拟嗜中性粒细胞溶酶体,用于单线态氧升高的癌症治疗

中性粒细胞是先天性免疫细胞向肿瘤组织迁移的第一线,可以立即杀死异常细胞并激活长期特异性适应性免疫反应。因此,中性粒细胞激发的酶介导的活性氧(ROS)升高可能是癌症免疫治疗中一种有前途的策略。在这里,我们通过表面磷酸酶触发氧化铁纳米颗粒周围的寡肽自组装来模拟生产中性粒细胞溶酶体的核壳超分子杂交纳米凝胶。受生物启发的纳米凝胶中超氧化物歧化酶(SOD)和氯过氧化物酶(CPO)的级联反应可将肿瘤组织中的ROS转化为次氯酸(HOCl)和随后的单线态氧(1O2)物种。
更新日期:2019-01-16
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