Abstract
Postoperative radiotherapy remains the gold standard for malignant glioma treatment. Clinical limitations, including tumor growth between surgery and radiotherapy and the emergence of radioresistance, reduce treatment effectiveness and result in local disease progression. This study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy. We developed a compound of carboplatin-loaded hydrogel (CPH) incorporated with carboplatin-loaded calcium carbonate (CPCC) to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model. The doses of carboplatin in CPH and CPCC treatments were 150 μL (carboplatin concentration of 5 mg/mL) and 15 mg (carboplatin concentration of 4.1 μg/mg), respectively. Mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation. Local CPH-CPCC delivery synergized effectively with limited-dose radiation to eliminate mouse glioma, offering a promising solution for overcoming clinical limitations.
Overview
- The study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy. The hypothesis being tested is that the combination of carboplatin-loaded hydrogel (CPH) and carboplatin-loaded calcium carbonate (CPCC) will synergize effectively with limited-dose radiation to eliminate malignant glioma in a C57BL/6 mouse subcutaneous tumor model. The methodology used for the experiment includes the development of a compound of CPH and CPCC to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model. The primary objective of the study is to evaluate the efficacy of the CPH-CPCC treatment in reducing tumor growth volume and progression-free survival compared to double-dose radiation alone. The study aims to provide a promising solution for overcoming clinical limitations in malignant glioma treatment.
Comparative Analysis & Findings
- The study compared the outcomes observed under two experimental conditions: double-dose radiation alone and the combination of CPH-CPCC treatment and limited-dose radiation (10 Gy in a single fraction). The results showed that mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation. These findings suggest that the CPH-CPCC treatment synergizes effectively with limited-dose radiation to eliminate malignant glioma in a C57BL/6 mouse subcutaneous tumor model.
Implications and Future Directions
- The study's findings suggest that the CPH-CPCC treatment synergizes effectively with limited-dose radiation to eliminate malignant glioma in a C57BL/6 mouse subcutaneous tumor model. This study provides a promising solution for overcoming clinical limitations in malignant glioma treatment. Future research directions could include evaluating the efficacy of the CPH-CPCC treatment in human malignant glioma models and investigating the optimal dosing and timing of the CPH-CPCC treatment for maximum efficacy. Additionally, further studies could explore the potential of the CPH-CPCC treatment in combination with other anticancer therapies, such as immunotherapy or chemotherapy, to enhance treatment efficacy.