PDF(Pubmed)
Abstract：
Boron neutron capture therapy (BNCT) is a unique radiotherapy of selectively eradicating tumor cells using boron compounds (e.g., 4-borono-L-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. Such heterogenicity potentially reduces the curative efficiency. However, the effects of temporospatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector and biophysical simulations, this study revealed the cell cycle-dependent heterogenicity of BPA uptake and subsequent biological effects of BNCT on HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators, as well as the modification effects of polyvinyl alcohol (PVA). The results showed that the BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA enhances the biological effects both by improving the uptake and by canceling the heterogenicity. These findings might contribute to a maximization of therapeutic efficacy when BNCT is combined with PVA and/or cell cycle-specific anticancer agents.
摘要：
硼中子俘获疗法（BNCT）是使用硼化合物选择性根除肿瘤细胞的独特放射疗法（例如，4-硼-L-苯丙氨酸[BPA]）在细胞水平上异质吸收。这种异质性潜在地降低了固化效率。然而,时空异质性对细胞杀伤的影响尚不清楚。通过辐射跟踪探测器和生物物理模拟的技术结合，这项研究揭示了BPA摄取的细胞周期依赖性异质性以及BNCT对HeLa细胞表达基于荧光泛素化的细胞周期指标的生物学效应，以及聚乙烯醇(PVA)的改性效果。结果表明，S/G2/M阶段的BPA浓度高于G1/S阶段，PVA通过提高吸收和消除异质性来增强生物学效应。当BNCT与PVA和/或细胞周期特异性抗癌剂组合时，这些发现可能有助于最大化治疗功效。
