Trienzyme-in-One Nanoparticle Making Multifunctional Synergistic Nanorobot for Tumor Therapy
文献类型： 外文期刊
作者： Gao, Zhixue 1 ; Yang, Zili 1 ; Luo, Ming 1 ; Pei, Ziye 1 ; Xu, Wentao 1 ; Liu, Yushan 1 ; Guo, Jie 1 ; Xiang, Xia 2 ; Yu, Zili 3 ; Zhao, Suling 1 ; Guan, Jianguo 1 ;
作者机构： 1.Wuhan Univ Technol, Int Sch Mat Sci & Engn, State Key Lab Adv Technol Mat Synth & Proc, Wuhan 430070, Peoples R China
2.Chinese Acad Agr Sci, Oil Crops & Lipids Proc Technol Natl & Local Joint, Oil Crops Res Inst, Wuhan 430062, Peoples R China
3.Wuhan Univ, Sch & Hosp Stomatol, State Key Lab Oral & Maxillofacial Reconstruct & R, Key Lab Oral Biomed,Minist Educ,Hubei Key Lab Stom, Wuhan 430079, Peoples R China
4.Wuhan Inst Photochem & Technol, Res Ctr Optoelectromagnet Funct Mat Technol, 7 North Bingang Rd, Wuhan 430083, Peoples R China
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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