Acridine orange inhibits pulmonary metastasis of mouse osteosarcoma
Haruhiko Satonaka1, Katsuyuki Kusuzaki, Koji Akeda
1Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu City, Mie, Japan.
Abstract:
Although the survival of patients with osteosarcoma has improved following development of chemotherapy and surgery, the presence of pulmonary metastases indicate a poor prognosis. We developed photodynamic and radiodynamic therapies with acridine orange (AO-PDT and AO-RDT) for minimally invasive surgery to treat musculoskeletal sarcomas and reported a good clinical outcome of local control and limb function. We investigated the effect of AO-PDT using flash-wave light (FWL) on pulmonary metastasis of mouse osteosarcoma. In in vitro and in vivo studies, AO alone and AO-PDT significantly inhibited cell invasion and the growth of pulmonary metastases from primary mouse osteosarcoma. AO may have a specific metastasis-inhibitory effect, different from the effect of AO-PDT. The fluorovisualization effect on pulmonary metastases following intravenous AO administration showed that pulmonary metastases localized on the lung surface were recognized as brilliant green lesions. In conclusion, AO-PDT using FWL inhibited cell invasion and pulmonary metastases in mouse osteosarcoma; therefore, this treatment modality might be applicable for treating pulmonary metastasis from malignant musculoskeletal tumors in humans.
Insights
Acridine orange photodynamic therapy (AO-PDT) with flash-wave light effectively inhibited osteosarcoma cell invasion and pulmonary metastasis in mice. This approach shows promise for treating metastatic bone cancers in humans.
Area of Science:
- Oncology
- Biomedical Engineering
- Photomedicine
Background:
- Osteosarcoma survival has improved, but pulmonary metastases still indicate a poor prognosis.
- Minimally invasive therapies are needed for musculoskeletal sarcomas, particularly for metastatic disease.
Purpose of the Study:
- To investigate the efficacy of acridine orange photodynamic therapy (AO-PDT) using flash-wave light (FWL) against pulmonary metastasis in a mouse osteosarcoma model.
- To evaluate the potential metastasis-inhibitory effects of acridine orange (AO) alone and AO-PDT.
Main Methods:
- In vitro and in vivo studies using a mouse osteosarcoma model.
- Administration of acridine orange (AO) and application of flash-wave light (FWL) for photodynamic therapy.
- Assessment of cell invasion and pulmonary metastasis growth, including fluorovisualization of metastases.
Main Results:
- Both AO alone and AO-PDT significantly inhibited osteosarcoma cell invasion.
- AO-PDT using FWL markedly reduced the growth of pulmonary metastases.
- Intravenous AO administration allowed for fluorovisualization of lung surface metastases as distinct green lesions.
Conclusions:
- AO-PDT with FWL demonstrates efficacy in inhibiting cell invasion and pulmonary metastasis of osteosarcoma in mice.
- Acridine orange may possess intrinsic metastasis-inhibitory properties.
- This therapy holds potential for treating pulmonary metastasis from human malignant musculoskeletal tumors.

