Trienzyme-in-One Nanoparticle Making Multifunctional Synergistic Nanorobot for Tumor Therapy
Zhixue Gao
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorZili Yang
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorCorresponding Author
Ming Luo
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorZiye Pei
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorWentao Xu
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorYushan Liu
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorJie Guo
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorXia Xiang
Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 China
Search for more papers by this authorZili Yu
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079 China
Search for more papers by this authorSuling Zhao
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorCorresponding Author
Jianguo Guan
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Research Center for Optoelectromagnetic Functional Materials Technology, Wuhan Institute of Photochemistry and Technology, 7 North Bingang Road, Wuhan, 430083 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorZhixue Gao
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorZili Yang
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorCorresponding Author
Ming Luo
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorZiye Pei
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorWentao Xu
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorYushan Liu
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorJie Guo
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorXia Xiang
Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 China
Search for more papers by this authorZili Yu
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079 China
Search for more papers by this authorSuling Zhao
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Search for more papers by this authorCorresponding Author
Jianguo Guan
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, International School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, 430070 China
Research Center for Optoelectromagnetic Functional Materials Technology, Wuhan Institute of Photochemistry and Technology, 7 North Bingang Road, Wuhan, 430083 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
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, ≈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 ≈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.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| smtd202500142-sup-0001-SuppMat.docx4.4 MB | Supporting Information |
| smtd202500142-sup-0002-VideoS1.mp46.8 MB | Supplemental Video 1 |
| smtd202500142-sup-0003-VideoS2.mp47.4 MB | Supplemental Video 2 |
| smtd202500142-sup-0004-VideoS3.mp46.7 MB | Supplemental Video 3 |
| smtd202500142-sup-0005-VideoS4.mp47 MB | Supplemental Video 4 |
| smtd202500142-sup-0006-VideoS5.mp42.9 MB | Supplemental Video 5 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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