[Image above] Live/Dead fluorescence images for osteosarcoma cells treated with 20 mg mL−1 conditioned media (10× magnification). Green (live), red (dead), scale bar equals 100 µm. Credit: Hanaei et al., Biomedical Materials (CC BY 4.0)
Learning you have cancer is an emotional experience. But medical advancements in the last few decades have made this diagnosis more manageable than before, and as a result, the U.S. cancer death rate has declined 33% since 1991.
However, improvements in cancer diagnosis and treatment are not equal across all kinds of cancer. For example, osteosarcoma is the most common primary bone cancer and affects primarily children and young adults. Survival rates for osteosarcoma increased significantly in the late 1970s and early 1980s with the development of chemotherapy. Since then, though, the five-year survival rate has plateaued, with current rates relatively static around 53–55%.
“Therefore, developing novel therapeutic platforms with high efficacy against primary [osteosarcoma] is crucial,” researchers write in an open-access paper.
The researchers come from Aston University in the U.K. In their paper, they explored the potential of using gallium-doped bioactive glasses as a treatment plan for osteosarcoma.
This choice of materials had a two-fold purpose. After a patient undergoes chemotherapy to treat the osteosarcoma, they are still at risk of local recurrence and also increased bone fractures due to the bone void caused by the tumor removal. These two concerns are usually delt with separately, but the gallium-doped bioactive glasses could potentially address both concerns at once.
First, gallium-based compounds are known for tumor suppression and so can help prevent local recurrence. However, there can be side effects from injecting this metal into the body, so localizing its delivery is preferable.
Bioactive glasses can be used for localized drug delivery. Additionally, these glasses have a widely recognized ability to foster the growth of bone cells, making them ideal for repair and regeneration applications.
Preliminary studies on gallium-doped bioactive glasses (here and here) helped slow the growth of osteosarcoma cancer cells. But given how rapidly cancer cells can multiply, “a significantly higher rate of kill is needed if these glasses are going to be a viable to treatment option,” the researchers write.
To achieve this higher killing rate, the researchers used rapid quenching techniques to extend the glass forming region of the bioactive glasses. This extension allowed them to have higher gallium concentrations in the glass.
Testing of the gallium-doped bioactive glasses using MTT viability assay kits resulted in 99% of the human-derived osteosarcoma cells being killed while the normal human osteoblasts were minimally affected.
The reason gallium significantly affected the cancerous cells and not the healthy ones is because of its effect on a cell’s iron uptake. Gallium forms complexes with transferrin receptors, which are the conventional pathway by which cells acquire iron for physiological requirements. Cancer cells are strongly dependent on iron for their growth and proliferation, so they are more sensitive to iron depletion when gallium forms complexes and blocks iron uptake.
In addition to suppressing tumor growth, the researchers observed that a layer of amorphous calcium phosphate/hydroxy apatite formed on the surface of the bioactive glass particulates after incubating in simulated body fluid—indicating the early stages of bone formation.
“The safety and effectiveness of these biomaterials will need to be tested further, but the initial results are really promising,” says coauthor Lucas Souza, research laboratory manager for the Dubrowsky Regenerative Medicine Laboratory at the Royal Orthopaedic Hospital, in an Aston University press release. “Research like this is vital to support in the development of new drugs and new methodologies for treatment options.”
The open-access paper, published in Biomedical Materials, is “Multifunctional gallium doped bioactive glasses: a targeted delivery for antineoplastic agents and tissue repair against osteosarcoma” (DOI: 10.1088/1748-605X/ad76f1).
Author
Lisa McDonald
CTT Categories
- Biomaterials & Medical