Malignant gliomas, predominantly glioblastoma and anaplastic astrocytoma, account for more than 70% of primary brain cancers in adults. Local recurrence remains high after tumor excision and concurrent chemoradiotherapy, leading to limited survival outcomes. The challenges in treating malignant glioma include: 1) tumor proliferation during the interval between surgery and radiotherapy, and 2) the radioresistance of tumor, coupled with the limited tolerance for radiation of brain, prevents completely eradicating the tumor with high doses. The critical questions in treating malignant glioma are: 1) how to inhibit tumor proliferation between interval of surgery and radiotherapy, and 2) how to enhance the anticancer effects of radiotherapy while limiting the radiation dose.
To meet these unmet clinical needs, we developed a novel local drug delivery system using carboplatin, an anticancer agent and radiosensitizer, to enhance radiotherapy efficacy. This system features a two-stage controlled-release mechanism using both hydrogel and particle (CaCO3) forms of carboplatin. Initially, the hydrogel releases a high concentration of carboplatin into the pericellular space to inhibit tumor proliferation before radiotherapy. After the hydrogel degrades, the carboplatin particles are internalized by cancer cells. Once the particles degrade in the acidic conditions of the endosome–lysosome or phagosome–lysosome complexes, they release condensed carboplatin intracellularly, which boosts the anticancer effects of subsequent radiotherapy.
Our innovative two-stage delivery system, using both hydrogel and particle forms of carboplatin, effectively inhibited initial tumor proliferation and synergized with subsequent limited-dose radiotherapy to eliminate malignant glioma in mice. Characterized by its precise temporal and spatial release, this local delivery system demonstrates significant potential for clinical impact and application in treating malignant gliomas.
Through a multidisciplinary collaboration between the Department of Biomedical Engineering at National Taiwan University and the Division of Radiation Oncology at National Taiwan University Hospital, we identified an unmet clinical need in malignant glioma treatment and devised a targeted engineering solution. Our research article is now available electronically on the Biomaterials journal website and is scheduled for publication in the January 2025 issue.
“As a radiation oncologist and neurologist, my goal is to enhance treatment efficacy and improve the quality of life for brain tumor patients,” said Dr. Liang. “In my role as a biomedical engineering scientist and educator, I am honored and committed to assembling multidisciplinary teams to enhance the effectiveness of brain tumor treatments and minimize their side effects.”
Link to the paper: https://www.sciencedirect.com/science/article/pii/S0142961224002801?via%3Dihub
