Related Experiment Video
Updated: Aug 11, 2025
Flexible Organic Electronic Devices for Pulsed Electric Field Therapy of Glioblastoma
Published on: August 9, 2022
Functional Graphene for Peritumoral Brain Microenvironment Modulation Therapy in Glioblastoma
Shan Min Chin1, Giacomo Reina2, Ngoc Do Quyen Chau2
1Emmanuel Gay, François Berger, INSERM UMR1205, Brain Tech Lab, Grenoble Alpes University, Grenoble, 38000, France.
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.
Insights
A novel graphene nanomaterial, reduced graphene oxide-polyethyleneimine (rGO-PEI), effectively combats glioblastoma invasion by neutralizing the peritumoral microenvironment and reducing pro-invasive factors.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Neuro-oncology
Background:
- Peritumoral brain invasion is a primary challenge in glioblastoma treatment, often leading to relapse.
- Current therapies like chemoradiotherapy and targeted treatments are insufficient due to brain inaccessibility, tumor heterogeneity, and the overlooked peritumor microenvironment.
Purpose of the Study:
- To develop a novel graphene-based nanomaterial for effective in vivo brain delivery and modulation of the glioblastoma microenvironment.
- To investigate the anti-invasive effects and mechanisms of the developed nanomaterial in a preclinical glioblastoma model.
Main Methods:
- Formulation of a highly water-stable reduced graphene oxide-polyethyleneimine (rGO-PEI) through ultramixing during functionalization.
- Assessment of brain diffusion and biocompatibility in mice.
- Evaluation of the anti-invasive effects using an invasive GL261 glioblastoma model.
- In vitro mechanistic studies using primary astrocytes and cytokine arrays.
Main Results:
- Demonstrated wide brain diffusion and biocompatibility of the rGO-PEI formulation.
- Observed a significant anti-invasive effect in the GL261 glioblastoma model.
- Reported neutralization of peritumoral gliosis and reduction of pro-inflammatory cytokines.
- Showed downregulation of pro-invasive/pro-tumoral cytokines at the tumor cell level.
Conclusions:
- The optimized rGO-PEI nanomaterial shows promise for in vivo brain delivery and glioblastoma microenvironment modulation.
- This new nanotherapy approach neutralizes astrogliosis and reduces key cytokines, offering a novel strategy against glioblastoma invasion.
