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Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model

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Radiodynamic Therapy for High-Grade Glioma in Normoxic and Hypoxic Environments for High-Grade Glioma.

Erika Yamada¹, Eiichi Ishikawa^1,2, Tsubasa Miyazaki³

¹Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Tsukuba 305-8576, Japan.

|December 30, 2025

Summary

Radiodynamic therapy (RDT) combining 5-aminolevulinic acid (5-ALA) and X-ray irradiation shows promise for high-grade glioma (HGG) under normoxia. Hypoxia limits RDT efficacy but may inhibit angiogenesis, warranting further research.

Keywords:

5-ALA glioma hypoxia immune reaction radiodynamic therapy

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Area of Science:

Oncology
Radiotherapy
Molecular Biology

Background:

High-grade glioma (HGG) presents therapeutic challenges.
Radiodynamic therapy (RDT), combining 5-aminolevulinic acid (5-ALA) and X-ray irradiation, is explored for HGG.
Understanding RDT efficacy across oxygen levels and its impact on the tumor microenvironment is crucial.

Purpose of the Study:

To evaluate the therapeutic potential of RDT for high-grade glioma (HGG).
To investigate RDT efficacy in normoxic and hypoxic conditions.
To elucidate RDT's mechanisms and effects on the tumor micro-immune environment.

Main Methods:

Experiments utilized human glioma cell lines (U87MG, U251MG) in vitro.
Cells were treated with or without 5-aminolevulinic acid (5-ALA) and X-ray irradiation.
Experiments were conducted under normoxic (20% O2) and hypoxic (3% O2) conditions.

Main Results:

RDT significantly reduced U87MG cell viability under normoxia via increased reactive oxygen species (ROS) production.
RDT efficacy was diminished under hypoxic conditions.
RDT modulated immune-related gene expression, epithelial-mesenchymal transition (EMT) genes, soluble PD-L1, VEGF, and CSF-1 secretion depending on oxygen levels.

Conclusions:

RDT, combining 5-ALA and X-ray irradiation, demonstrates therapeutic potential for HGG, particularly under normoxic conditions.
RDT may offer benefits under hypoxia, notably in inhibiting angiogenesis.
Oxygen levels critically influence RDT efficacy and its impact on the tumor microenvironment, necessitating further research for clinical optimization.