A self-directed Trojanbot-enzymatic nanobot in neutrobot for active target therapy of glioblastoma

Abstract Chemotherapy is an important treatment for glioblastoma (GBM) and a key component of comprehensive GBM therapy. However, the blood-brain barrier (BBB) and complex tumor microenvironment (TME) restrict the diffusion of drugs, which greatly reduces the chemotherapeutic effect on GBM. Single s...

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Main Authors: Yuanyuan Gao, Meng Mao, Yue Li, Mingjun Xuan, Yingjie Wu, Qiang He
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60422-z
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author Yuanyuan Gao
Meng Mao
Yue Li
Mingjun Xuan
Yingjie Wu
Qiang He
author_facet Yuanyuan Gao
Meng Mao
Yue Li
Mingjun Xuan
Yingjie Wu
Qiang He
author_sort Yuanyuan Gao
collection DOAJ
description Abstract Chemotherapy is an important treatment for glioblastoma (GBM) and a key component of comprehensive GBM therapy. However, the blood-brain barrier (BBB) and complex tumor microenvironment (TME) restrict the diffusion of drugs, which greatly reduces the chemotherapeutic effect on GBM. Single strategies, such as cell-based nanobots to cross the BBB or enzymatic nanobots propelled by enriched substrates in the TME for deep tumor penetration, remain inadequate to address multiple barriers and achieve precise targeting. Here, we develop a Trojan horse-inspired enzymatic nanobot-in-neutrobot system (Trojanbot) to greatly enhance targeted GBM therapy. Trojanbots traverse the BBB by leveraging positive chemotaxis in response to tumor-derived chemokine gradients, after which the released catalase-driven nanobots (CatNbot) undergo directional movement along the H2O2 gradients in TME, facilitating deep tumor penetration. This multi-stage targeting strategy improves drug delivery efficiency, providing considerable potential as a clinical approach for brain tumor treatment.
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issn 2041-1723
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publishDate 2025-06-01
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series Nature Communications
spelling doaj-art-c3a20b9357344dd39b43d255d49c50d52025-08-20T02:30:42ZengNature PortfolioNature Communications2041-17232025-06-0116112010.1038/s41467-025-60422-zA self-directed Trojanbot-enzymatic nanobot in neutrobot for active target therapy of glioblastomaYuanyuan Gao0Meng Mao1Yue Li2Mingjun Xuan3Yingjie Wu4Qiang He5Key Lab of Microsystems and Microstructures Manufacturing, School of Medicine and Health, Harbin Institute of TechnologyKey Lab of Microsystems and Microstructures Manufacturing, School of Medicine and Health, Harbin Institute of TechnologyKey Lab of Microsystems and Microstructures Manufacturing, School of Medicine and Health, Harbin Institute of TechnologyWenzhou Institute, University of Chinese Academy of SciencesKey Lab of Microsystems and Microstructures Manufacturing, School of Medicine and Health, Harbin Institute of TechnologyKey Lab of Microsystems and Microstructures Manufacturing, School of Medicine and Health, Harbin Institute of TechnologyAbstract Chemotherapy is an important treatment for glioblastoma (GBM) and a key component of comprehensive GBM therapy. However, the blood-brain barrier (BBB) and complex tumor microenvironment (TME) restrict the diffusion of drugs, which greatly reduces the chemotherapeutic effect on GBM. Single strategies, such as cell-based nanobots to cross the BBB or enzymatic nanobots propelled by enriched substrates in the TME for deep tumor penetration, remain inadequate to address multiple barriers and achieve precise targeting. Here, we develop a Trojan horse-inspired enzymatic nanobot-in-neutrobot system (Trojanbot) to greatly enhance targeted GBM therapy. Trojanbots traverse the BBB by leveraging positive chemotaxis in response to tumor-derived chemokine gradients, after which the released catalase-driven nanobots (CatNbot) undergo directional movement along the H2O2 gradients in TME, facilitating deep tumor penetration. This multi-stage targeting strategy improves drug delivery efficiency, providing considerable potential as a clinical approach for brain tumor treatment.https://doi.org/10.1038/s41467-025-60422-z
spellingShingle Yuanyuan Gao
Meng Mao
Yue Li
Mingjun Xuan
Yingjie Wu
Qiang He
A self-directed Trojanbot-enzymatic nanobot in neutrobot for active target therapy of glioblastoma
Nature Communications
title A self-directed Trojanbot-enzymatic nanobot in neutrobot for active target therapy of glioblastoma
title_full A self-directed Trojanbot-enzymatic nanobot in neutrobot for active target therapy of glioblastoma
title_fullStr A self-directed Trojanbot-enzymatic nanobot in neutrobot for active target therapy of glioblastoma
title_full_unstemmed A self-directed Trojanbot-enzymatic nanobot in neutrobot for active target therapy of glioblastoma
title_short A self-directed Trojanbot-enzymatic nanobot in neutrobot for active target therapy of glioblastoma
title_sort self directed trojanbot enzymatic nanobot in neutrobot for active target therapy of glioblastoma
url https://doi.org/10.1038/s41467-025-60422-z
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