Abstract
Successful treatment of glioblastoma (GBM) is hampered by primary tumor recurrence after surgical resection and poor prognosis, despite adjuvant radiotherapy and chemotherapy. In search of improved outcomes for this disease, quisinostat appeared as a lead compound in drug screening. A delivery system was devised for this drug and to exploit current clinical methodology: an injectable hydrogel, loaded with both the quisinostat drug and radiopaque gold nanoparticles (AuNP) as contrast agent, that can release these payloads as a response to radiation. This hydrogel grants high local drug concentrations, overcoming issues with current standards of care. Significant hydrogel degradation and quisinostat release were observed due to the radiation trigger, providing high in vitro anticancer activity. In vivo, the combination of radiotherapy and the radiation-induced delivery of quisinostat from the hydrogel, successfully inhibited tumor growth in a mice model bearing xenografted human GBM tumors with a total response rate of 67%. Long-term tolerability was observed after intratumoral injection of the quisinostat loaded hydrogel. The AuNP payload enabled precise image-guided radiation delivery and the monitoring of hydrogel degradation using computed tomography (CT). These exciting results highlight this hydrogel as a versatile imageable drug delivery platform that can be activated simultaneously to radiation therapy and potentially offers improved treatment for GBM.
Overview
- The study aims to investigate the potential of quisinostat as a lead compound for the treatment of glioblastoma (GBM) by developing a delivery system that can release the drug in response to radiation therapy. The study uses an injectable hydrogel loaded with quisinostat and radiopaque gold nanoparticles (AuNP) as a contrast agent. The hydrogel is designed to provide high local drug concentrations and overcome issues with current standards of care. The study's primary objective is to evaluate the in vitro and in vivo anticancer activity of the quisinostat-loaded hydrogel in a mice model bearing xenografted human GBM tumors. The study also aims to assess the long-term tolerability of the quisinostat-loaded hydrogel after intratumoral injection. The study's findings will contribute to the development of a versatile imageable drug delivery platform that can be activated simultaneously to radiation therapy and potentially offer improved treatment for GBM.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions, specifically the in vitro and in vivo anticancer activity of the quisinostat-loaded hydrogel. The study found significant hydrogel degradation and quisinostat release due to the radiation trigger, providing high in vitro anticancer activity. In vivo, the combination of radiotherapy and the radiation-induced delivery of quisinostat from the hydrogel successfully inhibited tumor growth in a mice model bearing xenografted human GBM tumors with a total response rate of 67%. The study's findings suggest that the quisinostat-loaded hydrogel has improved anticancer activity compared to current standards of care. The study also highlights the potential of the quisinostat-loaded hydrogel as a versatile imageable drug delivery platform that can be activated simultaneously to radiation therapy and potentially offer improved treatment for GBM.
Implications and Future Directions
- The study's findings have significant implications for the treatment of GBM, as they suggest that the quisinostat-loaded hydrogel has improved anticancer activity compared to current standards of care. The study's versatile imageable drug delivery platform has the potential to be activated simultaneously to radiation therapy and potentially offer improved treatment for GBM. The study identifies several limitations, including the need for further preclinical studies to assess the safety and efficacy of the quisinostat-loaded hydrogel in humans. The study suggests several future research directions, including the development of a clinical trial to evaluate the safety and efficacy of the quisinostat-loaded hydrogel in humans and the exploration of other drugs that can be delivered using this imageable drug delivery platform. The study also highlights the potential of the quisinostat-loaded hydrogel as a platform for the delivery of other drugs, such as immunotherapeutics, to improve treatment outcomes for GBM.