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.
Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases / Di Pompo, G; Kusuzaki, K; Ponzetti, M; Leone, VF; Baldini, N; Avnet, S. - In: BIOMEDICINES. - ISSN 2227-9059. - ELETTRONICO. - 10:8(2022), pp. 1904.1-1904.19. [10.3390/biomedicines10081904]
Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases
Di Pompo, G;Baldini, N;Avnet, S
2022
Abstract
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.File | Dimensione | Formato | |
---|---|---|---|
biomedicines-10-01904-v2 (1).pdf
accesso aperto
Tipo:
Versione (PDF) editoriale
Licenza:
Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione
3.73 MB
Formato
Adobe PDF
|
3.73 MB | Adobe PDF | Visualizza/Apri |
biomedicines-10-01904-s001.zip
accesso aperto
Tipo:
File Supplementare
Licenza:
Licenza per accesso libero gratuito
Dimensione
65.66 MB
Formato
Zip File
|
65.66 MB | Zip File | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.