Graphene Oxide Nanoscale Platform Enhances the Anti‐Cancer Properties of Bortezomib in Glioblastoma Models

• Published in: Advanced healthcare materials Vol. 12; no. 3; pp. e2201968 - n/a
• Main Authors: Sharp, Paul S., Stylianou, Maria, Arellano, Luis M., Neves, Juliana C., Gravagnuolo, Alfredo M., Dodd, Abbie, Barr, Katharine, Lozano, Neus, Kisby, Thomas, Kostarelos, Kostas
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-01-2023; John Wiley and Sons Inc
• Subjects: 2D materials; Animal models; Animals; Antineoplastic Agents - pharmacology; Bioavailability; Biological activity; Biomedical materials; Bortezomib; Bortezomib - therapeutic use; Brain cancer; Cell Line, Tumor; Chemotherapy; Cytotoxicity; Glioblastoma; Glioblastoma - pathology; Graphene; Graphite - chemistry; Localization; Mice; Microenvironments; Nanomaterials; nanomedicine; Nanosheets; Nanotechnology; Platforms; Proteasome inhibitors; Proteasomes; Sheets; Targeted cancer therapy; Tumor Microenvironment; Tumors; nanomedicine; glioblastoma; chemotherapy; graphene; 2D materials
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202201968

Graphene‐based 2D nanomaterials possess unique physicochemical characteristics which can be utilized in various biomedical applications, including the transport and presentation of chemotherapeutic agents. In glioblastoma multiforme (GBM), intratumorally administered thin graphene oxide (GO) nanosheets demonstrate a widespread distribution throughout the tumor volume without impact on tumor growth, nor spread into normal brain tissue. Such intratumoral localization and distribution can offer multiple opportunities for treatment and modulation of the GBM microenvironment. Here, the kinetics of GO nanosheet distribution in orthotopic GBM mouse models is described and a novel nano‐chemotherapeutic approach utilizing thin GO sheets as platforms to non‐covalently complex a proteasome inhibitor, bortezomib (BTZ), is rationally designed. Through the characterization of the GO:BTZ complexes, a high loading capacity of the small molecule on the GO surface with sustained BTZ biological activity in vitro is demonstrated. In vivo, a single low‐volume intratumoral administration of GO:BTZ complex shows an enhanced cytotoxic effect compared to free drug in two orthotopic GBM mouse models. This study provides evidence of the potential that thin and small GO sheets hold as flat nanoscale platforms for GBM treatment by increasing the bioavailable drug concentration locally, leading to an enhanced therapeutic effect.
Small, thin graphene oxide (GO) nanosheets undergo time‐dependent translocation and retention within the brain tumor microenvironment. GO nanosheets also offer a biocompatible, high‐surface‐area platform for the efficient non‐covalent complexation of chemotherapeutic agents. Loading GO with the proteasome inhibitor bortezomib (BTZ) provides improved efficacy and anti‐cancer activity following intratumoral administration in two orthotopic glioblastoma models.