Functional Graphene for Peritumoral Brain Microenvironment Modulation Therapy in Glioblastoma

Shan Min Chin, Giacomo Reina, Ngoc Do Quyen Chau, Tanguy Chabrol, Didier Wion, Ali Bouamrani, Emmanuel Gay, Yuta Nishina, Alberto Bianco, François Berger

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Peritumoral brain invasion is the main target to cure glioblastoma. Chemoradiotherapy and targeted therapies fail to combat peritumoral relapse. Brain inaccessibility and tumor heterogeneity explain this failure, combined with overlooking the peritumor microenvironment. Reduce graphene oxide (rGO) provides a unique opportunity to modulate the local brain microenvironment. Multimodal graphene impacts are reported on glioblastoma cells in vitro but fail when translated in vivo because of low diffusion. This issue is solved by developing a new rGO formulation involving ultramixing during the functionalization with polyethyleneimine (PEI) leading to the formation of highly water-stable rGO-PEI. Wide mice brain diffusion and biocompatibility are demonstrated. Using an invasive GL261 model, an anti-invasive effect is observed. A major unexpected modification of the peritumoral area is also observed with the neutralization of gliosis. In vitro, mechanistic investigations are performed using primary astrocytes and cytokine array. The result suggests that direct contact of rGO-PEIUT neutralizes astrogliosis, decreasing several proinflammatory cytokines that would explain a bystander tumor anti-invasive effect. rGO also significantly downregulates several proinvasive/protumoral cytokines at the tumor cell level. The results open the way to a new microenvironment anti-invasive nanotherapy using a new graphene nanomaterial that is optimized for in vivo brain delivery.

Original languageEnglish
Article number2208227
JournalSmall
Volume19
Issue number18
DOIs
Publication statusPublished - May 3 2023

Keywords

  • 2D materials
  • anti-invasion
  • astrocytes
  • cancer
  • chemical functionalization
  • macrophages

ASJC Scopus subject areas

  • General Chemistry
  • Engineering (miscellaneous)
  • Biotechnology
  • General Materials Science
  • Biomaterials

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