Cell-cycle dependence on the biological effects of boron neutron capture therapy and its modification by polyvinyl alcohol

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 e...

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Bibliographic Details
Published in:Scientific reports 2024-07, Vol.14 (1), p.16696-14, Article 16696
Main Authors: Matsuya, Yusuke, Sato, Tatsuhiko, Kusumoto, Tamon, Yachi, Yoshie, Seino, Ryosuke, Miwa, Misako, Ishikawa, Masayori, Matsuyama, Shigeo, Fukunaga, Hisanori
Format: Article
Language:English
Subjects:
631/57
631/80
639/705
Antineoplastic drugs
Atoms & subatomic particles
Biological effects
BNCT
Boron
Boron Compounds - pharmacology
Boron Neutron Capture Therapy - methods
BPA
Brain cancer
Cancer therapies
Cell culture
Cell cycle
Cell Cycle - drug effects
Cell Cycle - radiation effects
CR-39 detector
Health sciences
Heavy ions
HeLa Cells
Humanities and Social Sciences
Humans
Melanoma
Monte Carlo simulation
multidisciplinary
Neutrons
Phenylalanine
Phenylalanine - analogs & derivatives
Phenylalanine - pharmacology
Polyvinyl alcohol
Polyvinyl Alcohol - chemistry
PVA
Radiation
Radiation therapy
S phase
Science
Science (multidisciplinary)
Sensors
Tumor cells
Tumors
Ubiquitination
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Description
Summary: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/G 2 /M phase was higher than that in the G 1 /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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-67041-6