Electric field responsive nanotransducers for glioblastoma

Abstract

Background Electric field therapies such as Tumor Treating Fields (TTFields) have emerged as a bioelectronic treatment for isocitrate dehydrogenase wild-type and IDH mutant grade 4 astrocytoma Glioblastoma (GBM). TTFields rely on alternating current (AC) electric fields (EF) leading to the disruption of dipole alignment and induced dielectrophoresis (DEP) during cytokinesis. Although TTFields have a favourable side effect profile, particularly compared to cytotoxic chemotherapy, survival benefits remain limited (~ 4.9 months) after an extensive treatment regime (20 hours/day for 18 months). The cost of the technology also limits its clinical adoption worldwide. Therefore, the discovery of new technology that can enhance both the therapeutic efficiency and efficacy of these TTFields will be of great benefit to cancer treatment and decrease healthcare costs worldwide. Methods In this work, we report the role of electrically conductive gold (GNPs), dielectric silica oxide (SiO2), and semiconductor zinc oxide (ZnO) nanoparticles (NPs) as transducers for enhancing EF mediated anticancer effects on patient derived GBM cells. Physicochemical properties of these NPs were analyzed using spectroscopic, electron microscopy, and light-scattering techniques. Results In vitro TTFields studies indicated an enhanced reduction in the metabolic activity of patient-derived Glioma INvasive marginal (GIN 28) and Glioma contrast enhanced core (GCE 28) GBM As per our journal style, article titles should not include capitalised letters unless these are proper nouns/acronyms. We have therefore used the article title “Electric field responsive nanotransducers for glioblastoma” as opposed to “Electric Field Responsive Nanotransducers for Glioblastoma” as given in the submission system. Please check if this is correct.cells in groups treated with NPs vs. control groups, irrespective of NPs dielectric properties. Our results indicate the inorganic NPs used in this work enhance the intracellular EF effects that could be due to the virtue of bipolar dielectrophoretic and electrophoretic effects. Conclusions This work presents preliminary evidence which could help to improve future EF applications for bioelectronic medicine. Furthermore, the merits of spherical morphology, excellent colloidal stability, and low toxicity, make these NPs ideal for future studies for elucidating the detailed mechanism and efficacy upon their delivery in GBM preclinical models.

Tackling Anticancer Drug Resistance and Endosomal Escape in Aggressive Brain Tumors Using Bioelectronics

“…Another possible mechanism that could be considered is the behavior of GNPs as electric field transducers. 29 In this case, the polarization of GNPs in presence of AC could allow them to interact with plasma membrane in a way that facilitates their movements outwards. However, it is unclear how HF-AC could manipulate endosomal membrane, thus highlighting the need for new investigations on understanding the underlying mechanism such as AC mediated proton sponge effect.…”

“…18 Our group has recently shown that AC could bypass the plasma membrane to exert effects across the cell membrane. 16, 19 Moreover, it has been established that electrical input on lipid bilayers causes subtle structural perturbations in their structure. 20 Therefore, we hypothesized that by exploiting electrical input intracellular fate of nanoparticle-based delivery systems for anti-cancer therapy could be modulated.…”

Wireless Electrical-Molecular Quantum Signalling for Cancer Cell Induced Death

“…Importantly, the observed decrease of metabolic activity of GNP100@rC@Z treated cells was significantly higher than that following 24-hour application of FDA approved Tumour treating Fields (TTFs) in vitro . 28,29 We ascribe this significant decrease in metabolic activity to the electrical-molecular communication via redox switching of rC to oxidised form of C (oC), thus inducing cell stress. To eliminate any potential effect of applied 1 V on water electrolysis (1.23 V vs normal hydrogen electrode), we chose 0.65 V/cm for further studies.…”

Electric field distributions in realistic 3D rat head models during alternating electric field (AEF) therapy: a computational study

“…cancer) cells (Kirson et al 2007). The role of the intracellular anti-cancer properties of certain electrical fields, summarized as therapeutic alternating electrical fields or AEF are mediated by bipolar dielectrophoretic and electrophoretic effects (Kirson et al 2004, Jain et al 2022. Since the identification of this initial mechanism of action, multiple other mechanisms have been identified, ranging from permeabilization of cancer cell membranes (Chang et al 2018) to altered cancer cell metabolism (Patel et al 2021) and a modulation of immune response (Chen et al 2022, Lee et al 2022.…”