Functional Graphene for Peritumoral Brain Microenvironment Modulation Therapy in Glioblastoma

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-PEI_UT 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.     

Promising Perspectives on the Use of Fullerenes as Efficient Containers for Beryllium Atoms

The possibility of using fullerenes as containers for toxic beryllium atoms is studied by a multi-scale approach in which first-principles and classical molecular dynamics simulations are combined. By studying the energetics, electronic and spectroscopic properties of Be-fullerene systems and by simulating their interaction at finite temperature in vacuo and in representative biological environments it is concluded that: i) Be endohedral complexes can be obtained by implanting Be atoms at energies >2.3 eV that is consistent with laser implantation technologies; ii) it is in principle possible to distinguish stable endohedral complexes from metastable exohedral ones by optical absorption, suggesting that optical spectroscopy can be a valuable a non-destructive technique to assist the synthesis and the control of implanted films iii) the Be-endohedral complexes are long-lived and thermodynamically stable and can confine beryllium both in vacuo and in aqueous solution; iv) Be@C60 complexes are likely unable to penetrate the selectivity filters of a prototypical protein showing that fullerene prevents undesired interactions with biomolecules and toxicity effects of Be²⁺ related to replacement of the Ca²⁺. Overall, these results provide an assessment on the possibility to encapsulate Be atoms into fullerenes by ion implantation to synthesize inert and highly stable and safe molecular containers for toxic beryllium radionuclides. Great opportunities are expected for the realization and application of Be-C60 complexes to nanotechnology and nanomedicine with particularly appealing perspectives in the field of neutron capture therapy of cancer.     

Quantification of wind turbine energy loss due to leading-edge erosion through infrared-camera imaging,numerical simulations,and assessment against SCADA and meteorological data

Quantification of the performance degradation on the annual energy production (AEP) of a wind farm due to leading-edge (LE) erosion of wind turbine blades is important to design cost-effective maintenance plans and timely blade retrofit. In this work, the effects of LE erosion on horizontal axis wind turbines are quantified using infrared (IR) thermographic imaging of turbine blades, as well as meteorological and SCADA data. The average AEP loss of turbines with LE erosion is estimated from SCADA and meteorological data to be between 3% and 8% of the expected power capture. The impact of LE erosion on the average power capture of the turbines is found to be higher at lower hub-height wind speeds (peak around 50% of the turbine rated wind speed) and at lower turbulence intensity of the incoming wind associated with stable atmospheric conditions. The effect of LE erosion is investigated with IR thermography to identify the laminar to turbulent transition (LTT) position over the airfoils of the turbine blades. Reduction in the laminar flow region of about 85% and 87% on average in the suction and pressure sides, respectively, is observed for the airfoils of the investigated turbines with LE erosion. Using the observed LTT locations over the airfoils and the geometry of the blade, an average AEP loss of about 3.7% is calculated with blade element momentum simulations, which is found to be comparable with the magnitude of AEP loss estimated through the SCADA data.     

Mechanisms of Radical Formation on Chemically Modified Graphene Oxide under Near Infrared Irradiation

In this work, the mechanisms of radical generation on different functionalized graphene oxide (GO) conjugates under near-infrared (NIR) light irradiation are investigated. The GO conjugates are designed to understand how chemical functionalization can influence the generation of radicals. Both pristine and functionalized GO are irradiated by a NIR laser, and the production of different reactive oxygen species (ROS) is investigated using fluorimetry and electron paramagnetic resonance to describe the type of radicals present on the surface of GO. The mechanism of ROS formation involves a charge transfer from the material to the oxygen present in the media, via the production of superoxide and singlet oxygen. Cytotoxicity and effects of ROS generation are then evaluated using breast cancer cells, evidencing a concentration dependent cell death associated to the heat and ROS. The study provides new hints to understand the photogeneration of radicals on the surface of GO upon near infrared irradiation, as well as, to assess the impact on these radicals in the context of a combined drug delivery system and phototherapeutic approach. These discoveries open the way for a better control of phototherapy-based treatments employing graphene-based materials.