Open AccessNovel Treatment for Glioblastoma Delivered by a Radiation Responsive and Radiopaque Hydrogel
Author(s) -
Mathilde Bouché,
Yuxi C. Dong,
Saad Sheikh,
Kimberly Taing,
Deeksha Saxena,
Jessica C. Hsu,
Minna H. Chen,
Ryan Salinas,
Hongjun Song,
Jason A. Burdick,
Jay F. Dorsey,
David P. Cormode
Publication year - 2021
Publication title -
acs biomaterials science and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.082
H-Index - 50
ISSN - 2373-9878
DOI - 10.1021/acsbiomaterials.1c00385
Subject(s) - drug delivery , radiation therapy , in vivo , tolerability , medicine , drug , adjuvant , therapeutic index , biomedical engineering , self healing hydrogels , cancer research , materials science , pharmacology , oncology , surgery , nanotechnology , biology , microbiology and biotechnology , adverse effect , polymer chemistry
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.