ESTRO 2024 - Abstract Book

S5378

Radiobiology - Tumour biology

ESTRO 2024

Purpose/Objective:

Glioblastoma multiforme (GBM) is associated with a highly aggressive form of brain cancer. The death rate for GBM, is unfortunately quite high, and the survival rates are relatively low. Clinical treatment of glioblastoma typically involves a multidisciplinary approach, including surgery, radiation therapy, chemotherapy, but the prognosis is poor after the clinical treatment. In this study, we would like to investigate the effectiveness and convenience of treatment, combing thermosensitive and sustained-release nano-TiO2-loaded hydrogel with radiotherapy to facilitate the synergistic effect for GBM.

Material/Methods:

To demonstrate the characteristics of nano-TiO2 and the interaction of nano-TiO2 and radiation, we conduct WST-1, DCFDA assay and colony formation at mouse glioma cell (ALTS1C1), were determined to evaluate the toxicity, production of ROS and the synergistic effect of nano-TiO2 with radiation. In biomaterial, nano-TiO2-loaded hydrogel composed of hyaluronic acid / pluronic f-127, and hydrogel was tested by WST-1, rheometer, UV-VIS spectrophotometer to demonstrate the safety, thermosensitive and slow degradation. In ovo, Chorioallantoic Membrane Model (CAM) is used to evaluate the therapeutic effect of a combination treatment involving a thermosensitive sustained-release hydrogel loaded with nano-TiO2 and radiotherapy on the growth of glioblastoma. In vivo, we establish intracranial tumor animal models, ALTS1C1 cells were intracranially implanted in the specific position in the brain tissue of C57BL/6 mice. Hydrogel was administered via intertumoral injection, and RT was delivered after the drug delivery. In addition, we will use IVIS to monitor the progression of GBM. These experiments were crucial for studying the biology of brain cancer, which can evaluate potential treatments. All of the above experiments were categorized by Control (Ctrl), nano-TiO2-loaded hydrogel (Drug), radiotherapy (RT) and nano-TiO2 loaded hydrogel combine with radiotherapy (CCRT). WST-1 assay results indicate that there is no toxicity associated with nano-TiO2 and hyaluronic acid / pluronic f-127 hydrogel. Nano-TiO2, a photosensitive material. Based on the results of the DCFDA assay, it has been observed that when particles are exposed to radiation, they generate reactive oxygen species (ROS). These ROS molecules interact with and affect DNA. This interaction is believed to enhance the effects of radiotherapy. According to rheometer and UV-VIS spectrophotometer, Hyaluronic acid / pluronic f-127 hydrogel could undergo sol-gel transition at around 37 。 C(body temperature), and enable 24 hours drug release of nano-TiO2 before radiotherapy. Gradual release of nano TiO2 in order to improve its combined therapeutic effect when used in combination with radiotherapy. In CAM study, we observed favorable outcome related to size of tumors. Specifically, the statement suggests that tumor volume showed a positive response or change as a result of the study. Finally, the injectable hydrogel is aimed to apply on the tumor region intracranially in mouse, and give radiation therapy after 24 hours. The approach appears to be a combination therapy where the injectable hydrogel may have a specific purpose. Results:

Conclusion:

This study demonstrated that thermosensitive and sustained-release nano-TiO2-loaded hydrogel simplified intertumoral drug delivery and accomplish the synergistic effect with RT. The result suggests that nano-TiO2 is used to sensitize cancer cells to the effects of radiation, making the radiation therapy more effective in killing cancer cells.