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用于氧化癌症治疗的产过氧化氢溶瘤纳米反应器

Oncolytic Nanoreactors Producing Hydrogen Peroxide for Oxidative Cancer Therapy.

作者信息

Jo Seong-Min, Wurm Frederik R, Landfester Katharina

机构信息

Max Planck Institute for Polymer Research , Ackermannweg 10 , 55128 Mainz , Germany.

出版信息

Nano Lett. 2020 Jan 8;20(1):526-533. doi: 10.1021/acs.nanolett.9b04263. Epub 2019 Dec 9.

Abstract

generation of anticancer agents at the place of the disease is a new paradigm for cancer therapy. The production of highly potent drugs by nanoreactors through a facile synthesis pathway is demanded. We report an oncolytic nanoreactor platform loaded with the enzyme glucose oxidase (GOX) to produce hydrogen peroxide. For the first time, we realized a core-shell structure with encapsulated GOX under mild synthetic conditions, which ensured high remaining activity of GOX inside of the nanoreactor. Moreover, the nanoreactor protected the loaded GOX from proteolysis and contributed to increased thermal stability of the enzyme. The nanoreactors were effectively taken up into different cancer cells, in which they produced hydrogen peroxide by consuming intracellular glucose and oxygen, thereby leading to effective death of the cancer cells. In summary, our robust nanoreactors are a promising platform for effective anticancer therapy and sustained enzyme utilization.

摘要

在疾病发生部位生成抗癌剂是癌症治疗的一种新范式。需要通过简便的合成途径由纳米反应器生产高效药物。我们报道了一种负载葡萄糖氧化酶(GOX)以产生过氧化氢的溶瘤纳米反应器平台。我们首次在温和的合成条件下实现了包封GOX的核壳结构,这确保了纳米反应器内GOX的高残留活性。此外,纳米反应器保护负载的GOX不被蛋白水解,并有助于提高酶的热稳定性。纳米反应器被有效地摄取到不同的癌细胞中,在其中它们通过消耗细胞内的葡萄糖和氧气产生过氧化氢,从而导致癌细胞有效死亡。总之,我们强大的纳米反应器是有效抗癌治疗和持续酶利用的有前景的平台。

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