Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy

Pedrosa, Leire; Bedia, Carmen; Diao, Diouldé; Mosteiro, Alejandra; Ferrés, Abel; Stanzani, Elisabetta; Martínez‐Soler, Fina; Tortosa, Avelina; Pineda, Estela; Aldecoa, Ibán; Centellas, Marc; Muñoz-Tudurí, Marta; Sevilla, Ana; Sierra, Àngels; Sánchez, José Juan González

doi:10.3390/cells12081125

Cited by 8 publications

(4 citation statements)

References 51 publications

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“…Recent preclinical studies have also demonstrated the effectiveness of 5-ALA in treating glioblastoma within brain organoids, inducing cancer cell death while sparing healthy cells [130]. While this study focused on exploring the efficacy of 5-ALA to treat glioblastoma, their findings on the selective effectiveness in brain organoids provide a foundation (Figure 4).…”

Section: Pdt Applications In 3d Cancer Modelsmentioning

confidence: 99%

Current Advances in Photodynamic Therapy (PDT) and the Future Potential of PDT-Combinatorial Cancer Therapies

Alvarez,

Sevilla

2024

IJMS

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Photodynamic therapy (PDT) is a two-stage treatment that implies the use of light energy, oxygen, and light-activated compounds (photosensitizers) to elicit cancerous and precancerous cell death after light activation (phototoxicity). The biophysical, bioengineering aspects and its combinations with other strategies are highlighted in this review, both conceptually and as they are currently applied clinically. We further explore the recent advancements of PDT with the use of nanotechnology, including quantum dots as innovative photosensitizers or energy donors as well as the combination of PDT with radiotherapy and immunotherapy as future promising cancer treatments. Finally, we emphasize the potential significance of organoids as physiologically relevant models for PDT.

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Section: Pdt Applications In 3d Cancer Modelsmentioning

confidence: 99%

Current Advances in Photodynamic Therapy (PDT) and the Future Potential of PDT-Combinatorial Cancer Therapies

Alvarez,

Sevilla

2024

IJMS

Self Cite

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“…This finding supports the role of organoids as a reliable tool in reproducing the biology of original lesions, a finding that will be crucial for the future pipeline of therapeutic testing in GBM. For instance, Pedrosa and colleagues, who utilized a GBM organoid to test for the efficacy of photodynamic therapy with 5-aminolevulenic acid (5-ALA), showed that this model simulated 5-ALA uptake, protoporphyrin IX emission, and consequent GBM cell apoptosis in a dose-dependent manner [176]. In another study, Morelli et al utilized GBOs for metabolic imaging of the tumor's response to TMZ [177].…”

Section: Gbm-brain Organotypic Models (Gboms)mentioning

confidence: 99%

Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues

Slika,

Karimov,

Alimonti

et al. 2023

IJMS

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Glioblastoma is the most common malignant primary central nervous system tumor and one of the most debilitating cancers. The prognosis of patients with glioblastoma remains poor, and the management of this tumor, both in its primary and recurrent forms, remains suboptimal. Despite the tremendous efforts that are being put forward by the research community to discover novel efficacious therapeutic agents and modalities, no major paradigm shifts have been established in the field in the last decade. However, this does not mirror the abundance of relevant findings and discoveries made in preclinical glioblastoma research. Hence, developing and utilizing appropriate preclinical models that faithfully recapitulate the characteristics and behavior of human glioblastoma is of utmost importance. Herein, we offer a holistic picture of the evolution of preclinical models of glioblastoma. We further elaborate on the commonly used in vitro and vivo models, delving into their development, favorable characteristics, shortcomings, and areas of potential improvement, which aids researchers in designing future experiments and utilizing the most suitable models. Additionally, this review explores progress in the fields of humanized and immunotolerant mouse models, genetically engineered animal models, 3D in vitro models, and microfluidics and highlights promising avenues for the future of preclinical glioblastoma research.

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“…Thus, 5-ALA-based PDT can be a potential therapeutic strategy for the treatment of different tumors. In preclinical studies the anti-tumor efficacy of 5-ALA-mediated PDT has been observed in different cancer types such as skin cancer [ 30 ], esophageal cancer [ 31 ], colon cancer [ 28 ], human glioma [ 32 ], breast cancer [ 33 ], bladder cancer [ 34 ], and hepatocellular carcinoma [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of 5-Aminolevulinic Acid (5-ALA) in “ALADENT” Gel Formulation and Photodynamic Therapy (PDT) against Human Oral and Pancreatic Cancers

D’Antonio,

Marchetti,

Pignatelli

et al. 2024

Biomedicines

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Oral squamous-cell and pancreatic carcinomas are aggressive cancers with a poor outcome. Photodynamic therapy (PDT) consists of the use of photosensitizer-induced cell and tissue damage that is activated by exposure to visible light. PDT selectively acts on cancer cells, which have an accumulation of photosensitizer superior to that of the normal surrounding tissues. 5-aminolevulinic acid (5-ALA) induces the production of protoporphyrin IX (PpIX), an endogenous photosensitizer activated in PDT. This study aimed to test the effect of a new gel containing 5% v/v 5-ALA (ALAD-PDT) on human oral CAL-27 and pancreatic CAPAN-2 cancer cell lines. The cell lines were incubated in low concentrations of ALAD-PDT (0.05%, 0.10%, 0.20%, 0.40%, 0.75%, 1.0%) for 4 h or 8 h, and then irradiated for 7 min with 630 nm RED light. The cytotoxic effects of ALAD-PDT were measured using the MTS assay. Apoptosis, cell cycle, and ROS assays were performed using flow cytometry. PpIX accumulation was measured using a spectrofluorometer after 10 min and 24 and 48 h of treatment. The viability was extremely reduced at all concentrations, at 4 h for CAPAN-2 and at 8 h for CAL-27. ALAD-PDT induced marked apoptosis rates in both oral and pancreatic cancer cells. Elevated ROS production and appreciable levels of PpIX were detected in both cell lines. The use of ALA-PDT as a topical or intralesional therapy would permit the use of very low doses to achieve effective results and minimize side effects. ALAD-PDT has the potential to play a significant role in complex oral and pancreatic anticancer therapies.

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Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy

Cited by 8 publications

References 51 publications

Current Advances in Photodynamic Therapy (PDT) and the Future Potential of PDT-Combinatorial Cancer Therapies

Current Advances in Photodynamic Therapy (PDT) and the Future Potential of PDT-Combinatorial Cancer Therapies

Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues

Effect of 5-Aminolevulinic Acid (5-ALA) in “ALADENT” Gel Formulation and Photodynamic Therapy (PDT) against Human Oral and Pancreatic Cancers

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