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自组装单位点纳米酶可用于肿瘤特异性扩增级联酶促疗法
作者:小柯机器人 发布时间:2020/10/28 12:42:09

新加坡南洋理工大学Yanli Zhao等研究人员开发出自组装单位点纳米酶,可用于肿瘤特异性扩增级联酶促疗法。这一研究成果于2020年10月22日在线发表于国际学术期刊《德国应用化学》。

研究人员提出了一种新的策略,即通过开发针对肿瘤特异性疗法的单位点级联酶促反应,同时避免对正常组织的脱靶毒性。具有活性单位点铜的六氰合铁酸铜(Cu-HCF)纳米酶在肿瘤微环境中表现出级联酶活性(即谷胱甘肽氧化酶和过氧化物酶)。结果表明,Cu-HCF单位点纳米酶(SSNE)首先通过消耗细胞内的谷胱甘肽并将单点Cu II转化为Cu I来发挥肿瘤特异性谷胱甘肽氧化酶的能力,从而通过Fenton型Harber-Weiss反应随后放大过氧化物酶活性,最终产生大量的高毒性羟基自由基使得肿瘤细胞凋亡。
 
这项工作表明,SSNE可以增强单线态氧物种的杀伤力并抑制体内肿瘤的生长,从而为扩增级联酶促抗癌应用提供了一种有希望的自组装单位点纳米酶。
 
据介绍,具有模拟酶活性(纳米酶)的纳米材料是治疗干预的目标领域。然而,通过酶促反应选择性杀死肿瘤细胞,同时保持正常细胞不受损害,仍然是一个艰巨的挑战。
 
附:英文原文

Title: Self‐Assembled Single‐Site Nanozyme for Tumor‐Specific Amplified Cascade Enzymatic Therapy

Author: Yanli Zhao, Dongdong Wang, Huihui Wu, Changlai Wang, Long Gu, Hongzhong Chen, Deblin Jana, Xueying Wang, Pengping Xu, Zhen Guo, Qianwang Chen, Lili Feng, Jiawei Liu

Issue&Volume:

Abstract: Nanomaterials with enzyme‐mimicking activity (nanozyme) are at the targeted frontier for therapeutic interventions. However, it still remains a formidable challenge to selectively kill tumor cells through enzymatic reactions, while leaving normal cells unharmed. Herein, a new strategy is presented by developing single‐site cascade enzymatic reaction for tumor‐specific therapy while avoiding off‐target toxicity to normal tissues. Copper hexacyanoferrate (Cu‐HCF) nanozyme with active single‐site copper exhibits cascade enzymatic activity (i.e., glutathione oxidase and peroxidase) within tumor microenvironment. Results show that Cu‐HCF single‐site nanozymes (SSNEs) first exert tumor‐specific glutathione oxidase ability through depleting intracellular glutathione and converting single‐site CuII species to CuI for subsequent amplified peroxidase activity via Fenton‐type Harber‐Weiss reaction, and thus substantial highly toxic hydroxyl radicals are generated for tumor cell apoptosis. Our work demonstrates that SSNEs could amplify the killing efficacy of singlet oxygen species and suppress the tumor growth in vivo, providing a promising self‐assembled single‐site nanozyme for amplified cascade enzymatic anticancer application.

DOI: 10.1002/anie.202008868

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202008868

期刊信息

Angewandte Chemie:《德国应用化学》,创刊于1887年。隶属于德国化学会,最新IF:12.959
官方网址:https://onlinelibrary.wiley.com/journal/15213773
投稿链接:https://www.editorialmanager.com/anie/default.aspx