2403 - Radiosensitization Nanofiber Mesh for Synergistic Treatment of GBM Using Sustained Drug Release
Presenter(s)
M. Abulimiti1, Y. Sugawara2, Y. Li3, H. Sakurai4, and Y. Matsumoto5; 1Department of Radiation Oncology, Graduate School of Comprehensive Human Sciences, University of Tsukuba,Japan, TSUKUBA, Japan, 2Department of Radiation Oncology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan, Tsukuba, Japan, 3University of Tsukuba, Tsukuba City 305-8575, Ibaraki, Japan, 4Department of Radiation Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan, 5Proton Medical Research Center, University of Tsukuba Hospital, Tsukuba 305-8576, Japan;, Tsukuba, Japan
Purpose/Objective(s):
Glioblastoma is a highly aggressive brain tumor with limited therapeutic options and poor clinical outcomes. We developed a nanofiber mesh for sustained local delivery of chemotherapy and targeted agents to enhance postoperative radiotherapy through radiosensitization.Materials/Methods: A polycaprolactone-based nanofiber mesh co-loaded with temozolomide (TMZ) and the HSP90 inhibitor TAS116 was fabricated and characterized. Synergistic function and radiosensitizing effects were evaluated using in vitro cytotoxicity and colony-survival assays. In vivo glioblastoma models combined with drug-loaded nanofiber mesh and radiotherapy were also performed to explore the fiber-cytotoxic effect.
Results:
Synergy analysis demonstrated a synergistic interaction between TMZ and TAS116 across a wide range of concentrations, with a zip synergy score of 15.53. The colony assay showed that the IC50 of TAS-116 decreased from 2.05 µM to 0.45 µM when combined with TMZ, indicating synergistic cytotoxicity in U87MG cells. Following x-ray irradiation, combined TMZ and TAS116 treatment significantly enhanced radiosensitivity, yielding a synergy score of 39.01 (p = 0.009). Sensitization enhancement ratios (SERs) were 3.51 for TMZ and 1.80 for TAS116, confirming their radiosensitizing effects. The morphology and structural characteristics of PCL NFM were evaluated using scanning electron microscopy (SEM). It showed successful incorporation of TMZ and TAS116 into the PCL NFM while maintaining uniform fiber morphology and structural integrity. Drug release assays showed that 21.5% of TMZ and 40% of TAS116 were released within 24 hours, both exceeding their respective IC50 values. Both TMZ and TAS116-loaded PCL nanofiber meshes exhibited sustained drug release for more than 30 days and reached a cumulative release of approximately 45-50%. In vivo, drug-loaded PCL-NFM combined with radiotherapy markedly suppressed tumor growth and prolonged survival compared with the other treatment groups.Conclusion:
The combination of TMZ and TAS116 significantly enhanced radiosensitization. Drug-loaded nanofiber meshes enabled localized, sustained release above therapeutic thresholds, maintaining effective radiosensitizer levels within the tumor bed after surgical resection. As a biodegradable, implantable system, this strategy allows seamless integration with postoperative radiotherapy without the need for additional surgery, offering a clinically translatable approach to improve radiotherapy efficacy and overcome radioresistance in glioblastoma.