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<p>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 H<sub>2</sub>O<sub>2</sub> 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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月6日

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  • Yuanyuan Gao,
  • Meng Mao,
  • Yue Li,
  • Mingjun Xuan,
  • Yingjie Wu,
  • Qiang He

摘要

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.