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Introduction <p>Boron Neutron Capture Therapy (BNCT) offers precise tumor targeting in brain tumor treatment. However, its anti-glioma mechanism remains unclear, and radiation safety requires strict dose optimization.</p> Purpose <p>To define the safe therapeutic window for BNCT in the treatment of glioma and elucidate tumor-control mechanisms.</p> Methods <p> In vitro: GL261 cell viability assessed via CCK-8 and colony formation assays under varying <sup>10</sup>B-BPA concentrations and neutron irradiation durations. In vivo: Orthotopic GL261 glioma models established. Treatment efficacy evaluated by tumor weight, survival analysis, and body weight monitoring. Boron biodistribution measured by ICP-MS. Motor/cognitive function assessed via open field and novel object recognition tests. Key protein expression analyzed by Western blotting in tumors/normal brain tissue.</p> Results <p> In vitro, <sup>10</sup>B-BPA alone was non-cytotoxic, but significantly enhanced tumor cell killing when combined with neutron irradiation. In vivo, BNCT treatment (with <sup>10</sup>B-BPA dose of 250, [BNCT 250] or 500 mg/kg, [BNCT 500]) reduced tumor weight more effectively than neutron irradiation alone, confirming its enhanced anti-tumor effect. However, only the BNCT 250 alleviated motor impairment in mice. Photon-equivalent dose estimation revealed tumor/normal tissue biological doses of 4.43/1.42 Gy-Eq for BNCT 250 and 8.46/2.57 Gy-Eq for BNCT 500. Furthermore, BNCT 250 significantly increased NeuN and BDNF expression in normal brain tissue and promoted tumor apoptosis by elevating the Bax/Bcl-2 ratio, inducing cytochrome c release, and activating the caspase cascade.</p> Conclusion <p>Optimal BNCT regimen selectively triggered mitochondrial apoptosis in tumors <i>via</i> Bax/Bcl2/caspase cascade, while upregulating NeuN/BDNF in normal brains. This study firstly verified dual tumor control and neuroprotective efficacy of BNCT in vivo.</p>

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Dual tumor control and neuroprotective efficacy of Boron Neutron Capture Therapy in orthotopic mouse glioma model

  • 期刊论文

  • 发表日期：

    2025年11月6日

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  • Feifei Gao,
  • Hefa Huang,
  • Dashan Zuo,
  • Ruirong Zhuang,
  • Ningning Zheng,
  • Rui Quan,
  • Xiaohua Chen,
  • Haitao Huang,
  • Lu Zhang,
  • Zhongying Dai,
  • Weiqiang Chen,
  • Qiang Li

摘要

Introduction

Boron Neutron Capture Therapy (BNCT) offers precise tumor targeting in brain tumor treatment. However, its anti-glioma mechanism remains unclear, and radiation safety requires strict dose optimization.

Purpose

To define the safe therapeutic window for BNCT in the treatment of glioma and elucidate tumor-control mechanisms.

Methods

In vitro: GL261 cell viability assessed via CCK-8 and colony formation assays under varying 10B-BPA concentrations and neutron irradiation durations. In vivo: Orthotopic GL261 glioma models established. Treatment efficacy evaluated by tumor weight, survival analysis, and body weight monitoring. Boron biodistribution measured by ICP-MS. Motor/cognitive function assessed via open field and novel object recognition tests. Key protein expression analyzed by Western blotting in tumors/normal brain tissue.

Results

In vitro, 10B-BPA alone was non-cytotoxic, but significantly enhanced tumor cell killing when combined with neutron irradiation. In vivo, BNCT treatment (with 10B-BPA dose of 250, [BNCT 250] or 500 mg/kg, [BNCT 500]) reduced tumor weight more effectively than neutron irradiation alone, confirming its enhanced anti-tumor effect. However, only the BNCT 250 alleviated motor impairment in mice. Photon-equivalent dose estimation revealed tumor/normal tissue biological doses of 4.43/1.42 Gy-Eq for BNCT 250 and 8.46/2.57 Gy-Eq for BNCT 500. Furthermore, BNCT 250 significantly increased NeuN and BDNF expression in normal brain tissue and promoted tumor apoptosis by elevating the Bax/Bcl-2 ratio, inducing cytochrome c release, and activating the caspase cascade.

Conclusion

Optimal BNCT regimen selectively triggered mitochondrial apoptosis in tumors via Bax/Bcl2/caspase cascade, while upregulating NeuN/BDNF in normal brains. This study firstly verified dual tumor control and neuroprotective efficacy of BNCT in vivo.