Deep tissue translocation of graphene oxide sheets in human glioblastoma 3D spheroids and an orthotopic xenograft model
de Lázaro, Irene (University of Manchester. Nanomedicine Lab)
Sharp, Paul (University of Manchester. Nanomedicine Lab.)
Gurcan, Cansu (Ankara University. Department of Biomedical Engineering)
Ceylan, Ahmed (Ankara University. Faculty of Veterinary Medicine. Department of Histology Embryology)
Stylianou, Maria (University of Manchester. Nanomedicine Lab.)
Kisby, Thomas (University of Manchester. Nanomedicine Lab.)
Chen, Yingxian (University of Manchester. Nanomedicine Lab.)
Vranic, Sandra (University of Manchester. Nanomedicine Lab.)
Barr, Katharine (University of Manchester. Nanomedicine Lab.)
Taheri, Hadiseh (Ankara University. Department of Biomedical Engineering)
Ozen, Asuman (Ankara University. Faculty of Veterinary Medicine. Department of Histology Embryology)
Bussy, Cyrill (University of Manchester. Nanomedicine Lab.)
Yilmazer, Acelya (Ankara University. Department of Biomedical Engineering)
Kostarelos, Kostas (Institut Català de Nanociència i Nanotecnologia)

Data:	2021
Resum:	Its anatomical localization, a highly heterogeneous and drug-resistant tumor cell population and a "cold" immune microenvironment, all challenge the treatment of glioblastoma. Nanoscale drug delivery systems, including graphene oxide (GO) flakes, may circumvent some of these issues bypassing biological barriers, delivering multiple cargoes to impact several pathways simultaneously, or targeting the immune compartment. Here, the interactions of GO flakes with in vitro (U-87 MG three-dimensional spheroids, without stromal or immune compartments) and in vivo (U-87 MG orthotopic xenograft) models of glioblastoma are investigated. In vitro, GO flakes translocated deeply into the spheroids with little internalization in tumor cells. In vivo, intracranially administered GO also show extensive distribution throughout the tumor and demonstrate no impact on tumor growth and progression for the duration of the study. Internalization within tumor cells is also scarce, with the majority of flakes preferentially taken up by microglia/macrophages. The results indicate that GO flakes could offer deep and homogenous distribution throughout glioblastoma tumors and a means to target their myeloid compartment. Further studies are warranted to investigate the mechanisms of GO flakes transport within the tumor mass and their capacity to deliver bioactive cargoes but, ultimately, this information could inform the development of immunotherapies against glioblastoma.
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	2D materials ; Brain cancer ; Immunotherapy ; Macrophages ; Nanomedicine
Publicat a:	Advanced Therapeutics, Vol. 4, issue 1 (Jan. 2021) , art. 2000109, ISSN 2366-3987

DOI: 10.1002/adtp.202000109

15 p, 2.5 MB

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