Deep tissue translocation of graphene oxide sheets in human glioblastoma 3D spheroids and an orthotopic xenograft model

Irene De Lazaro Del Rey (Lead), Paul Sharp, Cansu Gurcan, Ahmet Ceylan, Maria Stylianou, Thomas Kisby, Yingxian Chen, Sandra Vranic, Katharine Barr, Hadiseh Taheri, Asuman Ozen, Cyrill Bussy, Acelya Yilmazer (Corresponding), Kostas Kostarelos (Corresponding)

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original languageEnglish
Article number2000109
JournalAdvanced Therapeutics
Volume4
Issue number1
Early online date9 Oct 2020
DOIs
Publication statusPublished - 20 Jan 2021

Keywords

  • graphene
  • cancer
  • Nanomedicine

Research Beacons, Institutes and Platforms

  • Advanced materials
  • Advanced Materials in Medicine
  • Lydia Becker Institute
  • National Graphene Institute

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-being

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