Graphene Oxide Nanoscale Platform Enhances the Anti-Cancer Properties of Bortezomib in Glioblastoma Models
Sharp, Paul S. (University of Manchester. Nanomedicine Lab)
Stylianou, Maria (University of Manchester. Nanomedicine Lab)
Arellano, Luis M. (Institut Català de Nanociència i Nanotecnologia)
Neves, Juliana C. (Institut Català de Nanociència i Nanotecnologia)
Gravagnuolo, Alfredo M. (University of Manchester. Nanomedicine Lab)
Dodd, Abbie (University of Manchester. Nanomedicine Lab)
Barr, Katharine (University of Manchester. Nanomedicine Lab)
Lozano, Neus (Institut Català de Nanociència i Nanotecnologia)
Kisby, Thomas (University of Manchester. Nanomedicine Lab)
Kostarelos, Kostas (Institut Català de Nanociència i Nanotecnologia)

Date:	2023
Abstract:	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.
Grants:	European Commission 881603 Agencia Estatal de Investigación SEV-2017-0706
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Advanced Healthcare Materials, Vol. 12, Issue 3 (January 2023) , art. 2201968, ISSN 2192-2659

DOI: 10.1002/adhm.202201968
PMID: 36300643

14 p, 4.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Catalan Institute of Nanoscience and Nanotechnology (ICN2)
Articles > Research articles
Articles > Published articles