Abstract | BACKGROUND: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy ( PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)-mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. METHODS: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. RESULTS: 5-ALA (50 and 100 µg/mL) was applied, and the release of protoporphyrin IX ( PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/ PDT on cancer cells without altering normal cells. CONCLUSIONS: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies.
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Authors | Leire Pedrosa, Carmen Bedia, Diouldé Diao, Alejandra Mosteiro, Abel Ferrés, Elisabetta Stanzani, Fina Martínez-Soler, Avelina Tortosa, Estela Pineda, Iban Aldecoa, Marc Centellas, Marta Muñoz-Tudurí, Ana Sevilla, Àngels Sierra, José Juan González Sánchez |
Journal | Cells
(Cells)
Vol. 12
Issue 8
(04 10 2023)
ISSN: 2073-4409 [Electronic] Switzerland |
PMID | 37190034
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Photosensitizing Agents
- Aminolevulinic Acid
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Topics |
- Humans
- Glioblastoma
(drug therapy, pathology)
- Photosensitizing Agents
(pharmacology, therapeutic use)
- Photochemotherapy
- Coculture Techniques
- Brain Neoplasms
(drug therapy, pathology)
- Cell Line, Tumor
- Aminolevulinic Acid
(pharmacology, therapeutic use)
- Glioma
(pathology)
- Brain
(pathology)
- Organoids
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