<br>锌基 ROS 放大器通过自级联催化触发癌症化学动力学/离子干扰疗法,Small

当前位置： X-MOL 学术 › Small › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

锌基 ROS 放大器通过自级联催化触发癌症化学动力学/离子干扰疗法
Small ( IF 13.0 ) Pub Date : 2024-06-16 , DOI: 10.1002/smll.202402320
Yun Sun ₁ , Liting Qin ₁ , Yuhan Yang ₁ , Jingzhe Gao ₁ , Yudi Zhang ₁ , Hongyu Wang ₁ , Qingyuan Wu ₁ , Bolong Xu ₁ , Huiyu Liu ₁

Affiliation

纳米酶介导的化疗动力学疗法由于其肿瘤特异性和受控的催化活性而成为一种很有前途的策略。然而，肿瘤微环境（TME）中低过氧化氢（H₂O₂）水平导致疗效不佳带来了挑战。在此，通过将类似过氧化物的活性铂纳米颗粒（Pt NPs）加载到过氧化锌（ZnO₂）（表示为 ZnO₂@Pt）上来构建 H₂O₂ 自供纳米酶。ZnO₂ 响应酸性 TME 释放 H₂O₂。Pt NPs 催化 H₂O₂ 产生羟基自由基，同时减少谷胱甘肽对氧化应激的缓解，通过自级联催化充当活性氧（ROS）放大器。此外，ZnO₂ 释放的 Zn²⁺ 会干扰肿瘤细胞的能量供应和代谢，使离子干扰疗法与化学动力学疗法协同作用。体外研究表明，ZnO₂@Pt 通过增强 ROS 生成和 Zn²⁺ 释放诱导细胞氧化应激损伤，下调 ATP 和 NAD⁺ 水平。体内抗癌作用评估表明，ZnO₂@Pt 可在肿瘤部位产生 ROS 以诱导细胞凋亡并下调与糖酵解相关的能量供应途径，导致肿瘤细胞生长减少 89.7%。本研究提出了一种能够进行 H₂O₂ 自我供应和离子干扰治疗的 TME 响应纳米酶，为肿瘤特异性纳米酶设计提供了一种范式。

"点击查看英文标题和摘要"

Zinc-Based ROS Amplifiers Trigger Cancer Chemodynamic/Ion Interference Therapy Through Self-Cascade Catalysis

Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H₂O₂) levels in the tumor microenvironment (TME) poses challenges. Herein, an H₂O₂ self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO₂) (denoted as ZnO₂@Pt). ZnO₂ releases H₂O₂ in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H₂O₂ while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn²⁺ released from ZnO₂ interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO₂@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn²⁺ release, downregulating ATP and NAD⁺ levels. In vivo assessment of anticancer effects showed that ZnO₂@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H₂O₂ self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.

更新日期：2024-06-16

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南