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Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases
Current multimodal treatment of bone metastases is partially effective and often associated with side effects, and novel therapeutic options are needed. Acridine orange is a photosensitizing molecule that accumulates in acidic compartments. After photo- or radiodynamic activation (AO-PDT or AO-RDT),...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405350/ https://www.ncbi.nlm.nih.gov/pubmed/36009451 http://dx.doi.org/10.3390/biomedicines10081904 |
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author | Di Pompo, Gemma Kusuzaki, Katsuyuki Ponzetti, Marco Leone, Vito Ferdinando Baldini, Nicola Avnet, Sofia |
author_facet | Di Pompo, Gemma Kusuzaki, Katsuyuki Ponzetti, Marco Leone, Vito Ferdinando Baldini, Nicola Avnet, Sofia |
author_sort | Di Pompo, Gemma |
collection | PubMed |
description | Current multimodal treatment of bone metastases is partially effective and often associated with side effects, and novel therapeutic options are needed. Acridine orange is a photosensitizing molecule that accumulates in acidic compartments. After photo- or radiodynamic activation (AO-PDT or AO-RDT), acridine orange can induce lysosomal-mediated cell death, and we explored AO-RDT as an acid-targeted anticancer therapy for bone metastases. We used osteotropic carcinoma cells and human osteoclasts to assess the extracellular acidification and invasiveness of cancer cells, acridine orange uptake and lysosomal pH/stability, and the AO-RDT cytotoxicity in vitro. We then used a xenograft model of bone metastasis to compare AO-RDT to another antiacid therapeutic strategy (omeprazole). Carcinoma cells showed extracellular acidification activity and tumor-derived acidosis enhanced cancer invasiveness. Furthermore, cancer cells accumulated acridine orange more than osteoclasts and were more sensitive to lysosomal death. In vivo, omeprazole did not reduce osteolysis, whereas AO-RDT promoted cancer cell necrosis and inhibited tumor-induced bone resorption, without affecting osteoclasts. In conclusion, AO-RDT was selectively toxic only for carcinoma cells and effective to impair both tumor expansion in bone and tumor-associated osteolysis. We therefore suggest the use of AO-RDT, in combination with the standard antiresorptive therapies, to reduce disease burden in bone metastasis. |
format | Online Article Text |
id | pubmed-9405350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94053502022-08-26 Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases Di Pompo, Gemma Kusuzaki, Katsuyuki Ponzetti, Marco Leone, Vito Ferdinando Baldini, Nicola Avnet, Sofia Biomedicines Article Current multimodal treatment of bone metastases is partially effective and often associated with side effects, and novel therapeutic options are needed. Acridine orange is a photosensitizing molecule that accumulates in acidic compartments. After photo- or radiodynamic activation (AO-PDT or AO-RDT), acridine orange can induce lysosomal-mediated cell death, and we explored AO-RDT as an acid-targeted anticancer therapy for bone metastases. We used osteotropic carcinoma cells and human osteoclasts to assess the extracellular acidification and invasiveness of cancer cells, acridine orange uptake and lysosomal pH/stability, and the AO-RDT cytotoxicity in vitro. We then used a xenograft model of bone metastasis to compare AO-RDT to another antiacid therapeutic strategy (omeprazole). Carcinoma cells showed extracellular acidification activity and tumor-derived acidosis enhanced cancer invasiveness. Furthermore, cancer cells accumulated acridine orange more than osteoclasts and were more sensitive to lysosomal death. In vivo, omeprazole did not reduce osteolysis, whereas AO-RDT promoted cancer cell necrosis and inhibited tumor-induced bone resorption, without affecting osteoclasts. In conclusion, AO-RDT was selectively toxic only for carcinoma cells and effective to impair both tumor expansion in bone and tumor-associated osteolysis. We therefore suggest the use of AO-RDT, in combination with the standard antiresorptive therapies, to reduce disease burden in bone metastasis. MDPI 2022-08-05 /pmc/articles/PMC9405350/ /pubmed/36009451 http://dx.doi.org/10.3390/biomedicines10081904 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Di Pompo, Gemma Kusuzaki, Katsuyuki Ponzetti, Marco Leone, Vito Ferdinando Baldini, Nicola Avnet, Sofia Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases |
title | Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases |
title_full | Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases |
title_fullStr | Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases |
title_full_unstemmed | Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases |
title_short | Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases |
title_sort | radiodynamic therapy with acridine orange is an effective treatment for bone metastases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405350/ https://www.ncbi.nlm.nih.gov/pubmed/36009451 http://dx.doi.org/10.3390/biomedicines10081904 |
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