Hypoxia-instructed pro-protein therapy assisted with self-catalyzed nanozymogen.,Angewandte Chemie International Edition

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Hypoxia-instructed pro-protein therapy assisted with self-catalyzed nanozymogen.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-06-20 , DOI: 10.1002/anie.202004008
Xudong Li ₁ , Yuansong Wei ₁ , Yuchen Wu ₁ , Lichen Yin ₁

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The success of intracellular protein therapy demands efficient delivery and selective protein activity in diseased cells. Therefore, a cascaded nanozymogen consisting of a hypoxia‐activatable pro‐protein, a hypoxia‐inducing protein, and a hypoxia‐strengthened intracellular protein delivery nanovehicle was developed. RPAB, an enzymatically inactive pro‐protein of RNase, reversibly caged with hypoxia‐cleavable azobenzene, was delivered with glucose oxidase (GOx) using hypoxia‐responsive nanocomplexes (NCs) consisting of azobenzene‐cross‐linked oligoethylenimine (AOEI) and hyaluronic acid (HA). Upon NC‐mediated delivery into cancer cells, GOx catalyzed glucose decomposition and aggravated tumoral hypoxia, which drove the recovery of RPAB back to the hydrolytically active RNase and expedited the degradation of AOEI to release more protein cargoes. Thus, the catalytic reaction of the nanozymogen was self‐accelerated and self‐cycled, ultimately leading to a cooperative anti‐cancer effect between GOx‐mediated starvation therapy and RNase‐mediated pro‐apoptotic therapy.

中文翻译：

缺氧指导的前蛋白治疗辅助自催化纳米酶原。

细胞内蛋白质治疗的成功需要在患病细胞中有效递送和选择性蛋白质活性。因此，开发了一种级联纳米酶原，它由缺氧可激活的前蛋白、缺氧诱导蛋白和缺氧强化的细胞内蛋白质递送纳米载体组成。RPAB 是一种酶促无活性的 RNase 前蛋白，与低氧可裂解的偶氮苯可逆地结合，使用由偶氮苯交联的低聚亚乙基亚胺 (AOEI) 和透明质酸组成的缺氧响应纳米复合物 (NCs) 与葡萄糖氧化酶 (GOx) 一起递送。哈）。在 NC 介导的递送到癌细胞后，GOx 催化葡萄糖分解并加剧肿瘤缺氧，这促使 RPAB 恢复为具有水解活性的 RNase，并加速 AOEI 的降解以释放更多的蛋白质货物。

更新日期：2020-06-20

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