Novel intravenous formulation for radiosensitization in osteosarcoma treatment

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Oncology

Background:

• Osteosarcoma (OS) is a primary bone cancer in children and adolescents with limited radiotherapy efficacy.
• Radiotherapy resistance is exacerbated by tumor hypoxia and immunosuppression.
• Current hafnium oxide radiosensitizers require intratumoral administration, limiting treatment options for intraosseous tumors.

Purpose of the Study:

• To develop an intravenous formulation of hafnium oxide for enhanced osteosarcoma radiosensitivity.
• To investigate a synergistic therapeutic approach combining radiosensitization, photothermal therapy, and immune activation.
• To overcome limitations in current osteosarcoma radiotherapy.

Main Methods:

• Synthesized hafnium-doped Prussian blue nanoparticles (HP) coated with a tannic acid-manganese metallophenol network (HPTM).
• Administered HPTM intravenously in a murine model of osteosarcoma with lung metastases.
• Evaluated HPTM's tumor localization, manganese release, STING pathway activation, photothermal effect, and radiosensitizing properties under X-ray irradiation.

Main Results:

• HPTM effectively localized to primary OS tumors after intravenous injection.
• Manganese release activated the STING pathway, inducing anti-tumor immune responses.
• HPTM combined with near-infrared light and X-ray irradiation significantly increased apoptosis, reduced lung metastases, and suppressed tumor growth in radiotherapy-resistant OS.
• Generated reactive oxygen species and induced DNA damage in tumor cells.

Conclusions:

• HPTM is a promising intravenous radiosensitizer for osteosarcoma.
• The synergistic approach integrates radiosensitization, photothermal therapy, and STING pathway activation.
• This strategy offers a potential clinical translation to improve osteosarcoma radiotherapy outcomes.