Purpose

Boron neutron capture therapy (BNCT) is a tumor cell-selective particle-radiation therapy. In BNCT, administered p-boronophenylalanine (BPA) is selectively taken up by tumor cells, and the tumor is irradiated with thermal neutrons. High-LET α-particles and recoil ⁷Li, which have a path length of 5–9 μm, are generated by the capture reaction between ¹⁰B and thermal neutrons and selectively kill tumor cells that have uptaken ¹⁰B. Although BNCT has prolonged the survival time of malignant glioma patients, recurrences are still to be resolved. miRNAs, that are encapsulated in small extracellular vesicles (sEVs) in body fluids and exist stably may serve critical role in recurrence. In this study, we comprehensively investigated microRNAs (miRNAs) in sEVs released from post-BNCT glioblastoma cells.

Method

Glioblastoma U87 MG cells were treated with 25 ppm of BPA in the culture media and irradiated with thermal neutrons. After irradiation, they were plated into dishes and cultured for 3 days in the 5% CO₂ incubator. Then, sEVs released into the medium were collected by column chromatography, and miRNAs in sEVs were comprehensively investigated using microarrays.

Result

An increase in 20 individual miRNAs (ratio > 2) and a decrease in 2 individual miRNAs (ratio < 0.5) were detected in BNCT cells compared with non-irradiated cells. Among detected miRNAs, 20 miRNAs were associated with worse prognosis of glioma in Kaplan Meier Survival Analysis of overall survival in TCGA.

Conclusion

These miRNA after BNCT may proceed tumors, modulate radiation resistance, or inhibit invasion and affect the prognosis of glioma.

中文翻译：

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硼中子捕获疗法处理的胶质母细胞瘤细胞释放的小细胞外囊泡中 miRNA 的分布

目的

硼中子捕获疗法（BNCT）是一种肿瘤细胞选择性粒子放射疗法。在BNCT中，给予的对硼苯丙氨酸（BPA）被肿瘤细胞选择性吸收，并用热中子照射肿瘤。高LET α粒子和反冲⁷ Li，其路径长度为5-9μm，是由¹⁰ B与热中子之间的俘获反应产生的，并选择性地杀死摄取¹⁰ B的肿瘤细胞。恶性胶质瘤患者的生存时间、复发情况仍有待解决。 miRNA 封装在体液中的小细胞外囊泡 (sEV) 中并稳定存在，可能在复发中发挥关键作用。在这项研究中，我们全面研究了 BNCT 后胶质母细胞瘤细胞释放的 sEV 中的 microRNA (miRNA)。

方法

胶质母细胞瘤 U87 MG 细胞在培养基中用 25 ppm BPA 处理，并用热中子照射。照射后，将它们接种到培养皿中并在5%CO ₂培养箱中培养3天。然后，通过柱色谱收集释放到培养基中的sEV，并使用微阵列全面研究sEV中的miRNA。

结果

与未照射细胞相比，BNCT 细胞中检测到 20 个个体 miRNA（比率 > 2）增加和 2 个个体 miRNA（比率 < 0.5）减少。在 TCGA 总体生存的 Kaplan Meier 生存分析中，检测到的 miRNA 中，有 20 个 miRNA 与神经胶质瘤的较差预后相关。

结论

BNCT后的这些miRNA可能会促进肿瘤、调节放射抵抗或抑制侵袭并影响胶质瘤的预后。