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Glioblastoma Relapse Post-Resection Model for Therapeutic Hydrogel Investigations
Published on: February 24, 2023
Novel Treatment for Glioblastoma Delivered by a Radiation Responsive and Radiopaque Hydrogel
Mathilde Bouché1, Yuxi C Dong1,2, Saad Sheikh3
1Department of Radiology, University of Pennsylvania, 3400 Spruce Street, 1 Silverstein Philadelphia, Pennsylvania 19104, United States.
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.
Insights
A novel hydrogel loaded with quisinostat and gold nanoparticles (AuNP) offers improved glioblastoma (GBM) treatment. Radiation triggers drug release, inhibiting tumor growth and enabling image-guided therapy.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Glioblastoma (GBM) treatment faces challenges with tumor recurrence and poor prognosis.
- Current therapies like radiotherapy and chemotherapy have limitations in efficacy and delivery.
- Quisinostat shows promise as a lead compound for GBM treatment.
Purpose of the Study:
- To develop an injectable hydrogel drug delivery system for quisinostat in GBM treatment.
- To integrate gold nanoparticles (AuNP) for image-guided radiation delivery and monitoring.
- To evaluate the efficacy and safety of radiation-triggered quisinostat release from the hydrogel.
Main Methods:
- An injectable hydrogel loaded with quisinostat and AuNP was synthesized.
- Hydrogel degradation and drug release kinetics were studied in response to radiation.
- In vitro anticancer activity was assessed.
- In vivo efficacy was evaluated in a murine GBM xenograft model.
- Image guidance and monitoring were performed using computed tomography (CT).
Main Results:
- Radiation triggered significant hydrogel degradation and quisinostat release.
- High in vitro anticancer activity was observed.
- The combination therapy inhibited tumor growth in vivo, achieving a 67% response rate.
- Intratumoral injection demonstrated long-term tolerability.
- AuNP enabled precise image-guided radiation and hydrogel degradation monitoring via CT.
Conclusions:
- The developed hydrogel is a versatile, imageable drug delivery platform for GBM.
- Radiation-activated quisinostat release enhances local drug concentration and therapeutic efficacy.
- This platform holds potential for improved glioblastoma treatment strategies when combined with radiotherapy.
