Trienzyme-in-One Nanoparticle Making Multifunctional Synergistic Nanorobot for Tumor Therapy

文献类型： 外文期刊

第一作者： Gao, Zhixue

作者： Gao, Zhixue;Yang, Zili;Luo, Ming;Pei, Ziye;Xu, Wentao;Liu, Yushan;Guo, Jie;Zhao, Suling;Guan, Jianguo;Xiang, Xia;Yu, Zili;Guan, Jianguo

作者机构：

关键词： enzyme; nanorobot; selective toxicity; synergistic therapy; tumor penetration

期刊名称：SMALL METHODS （ 影响因子：9.1； 五年影响因子：10.5 ）

ISSN： 2366-9608

年卷期： 2025 年 9 卷 8 期

页码：

收录情况： SCI

摘要： Current nanoparticle-based drug delivery systems for tumor therapy face significant challenges in intratumoral penetration and cellular internalization, leading to poor therapeutic efficacy. Herein, it is demonstrated that the sequential integration of glucose oxidase (GOx), catalase (CAT), and urease (URE) onto the half surface of biotin-modified Janus nanoparticles via the chemical coupling way produces nanorobots of multifunctionality and synergistic effect (denoted as UCGPJNRs). They can autonomously and powerfully move in tumor microenvironment (TME) by using endogenous urea as a fuel, enabling to penetrate deeper than 0.55 mm into tumor tissues, approximate to 5.5-fold of the previous counterparts. The UCGPJNRs perform motion-enhanced biotin receptor-mediated endocytosis and endoplasmic reticulum/Golgi apparatus pathway-mediated exocytosis, greatly improving the internalization efficiency of tumor cells. They release NH3 when moving to produce selective toxicity against tumor cells in hypoxic TME. Further, they enhance the glucose consumption by approximate to three times due to the motion-accelerated GOx/CAT cascade reaction, disrupting the metabolism against tumor cells on a large area. After intratumorally injecting into tumor-bearing mice, UCGPJNRs can significantly amplify the in vivo tumor growth inhibition rate through their synergistic effect. This work provides a plausible strategy to overcome current limitations in tumor treatment by anchoring multiple bioenzymes on one nanoparticle.

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