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

Yuanyuan Gao, Meng Mao (), Yue Li, Mingjun Xuan, Yingjie Wu () and Qiang He ()
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Yuanyuan Gao: Harbin Institute of Technology
Meng Mao: Harbin Institute of Technology
Yue Li: Harbin Institute of Technology
Mingjun Xuan: University of Chinese Academy of Sciences
Yingjie Wu: Harbin Institute of Technology
Qiang He: Harbin Institute of Technology

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60422-z

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