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铁离子驱动的过氧化氢酶样超分子光酶纳米酶组装用于缺氧肿瘤的治疗。

Ferric Ion Driven Assembly of Catalase-like Supramolecular Photosensitizing Nanozymes for Combating Hypoxic Tumors.

机构信息

Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.

CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.

出版信息

Angew Chem Int Ed Engl. 2020 Dec 14;59(51):23228-23238. doi: 10.1002/anie.202010005. Epub 2020 Oct 15.

Abstract

A facile approach to assemble catalase-like photosensitizing nanozymes with a self-oxygen-supplying ability was developed. The process involved Fe -driven self-assembly of fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids. By adding a zinc(II) phthalocyanine-based photosensitizer (ZnPc) and the hypoxia-inducible factor 1 (HIF-1) inhibitor acriflavine (ACF) during the Fe -promoted self-assembly of Fmoc-protected cysteine (Fmoc-Cys), the nanovesicles Fmoc-Cys/Fe@Pc and Fmoc-Cys/Fe@Pc/ACF were prepared, which could be disassembled intracellularly. The released Fe could catalyze the transformation of H O enriched in cancer cells to oxygen efficiently, thereby ameliorating the hypoxic condition and promoting the photosensitizing activity of the released ZnPc. With an additional therapeutic component, Fmoc-Cys/Fe@Pc/ACF exhibited higher in vitro and in vivo photodynamic activities than Fmoc-Cys/Fe@Pc, demonstrating the synergistic effect of ZnPc and ACF.

摘要

一种简便的方法被开发出来,用于组装具有自供氧能力的类过氧化氢酶光纳米酶。该过程涉及 Fe 驱动的芴甲氧羰基(Fmoc)保护的氨基酸的自组装。通过在 Fe 促进的 Fmoc-保护半胱氨酸(Fmoc-Cys)的自组装过程中添加锌(II)酞菁类光敏剂(ZnPc)和缺氧诱导因子 1(HIF-1)抑制剂吖啶黄素(ACF),可以制备纳米囊泡 Fmoc-Cys/Fe@Pc 和 Fmoc-Cys/Fe@Pc/ACF,它们可以在细胞内解体。释放的 Fe 可以有效地将富含癌细胞的 H 2 O 转化为氧气,从而改善缺氧状态并促进释放的 ZnPc 的光动力活性。由于增加了治疗成分,Fmoc-Cys/Fe@Pc/ACF 在体外和体内的光动力活性均高于 Fmoc-Cys/Fe@Pc,证明了 ZnPc 和 ACF 的协同作用。

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