In our ongoing battle against aggressive brain tumours like glioblastoma and medulloblastoma, drug resistance presents a persistent and formidable challenge. Conventional chemotherapy often falls short as these cancer cells develop ways to trap or expel drugs, reducing their effectiveness. However, in our recent research at the University of Nottingham, we’ve made significant strides in tackling this issue by combining electrical treatment with advanced cancer therapeutics (Jain et al., 2024) here.
Understanding Drug Resistance and Endosomal Escape
Brain tumours frequently develop resistance by trapping therapeutic agents within endosomes or expelling them through extracellular vesicles (EVs). This barrier is especially problematic for nanoparticle-based drug delivery systems, where therapeutic nanoparticles often become confined and inactive.
Our study explored how alternating current (AC) electrical stimulation can effectively disrupt these resistance mechanisms. By combining gold nanoparticles (GNPs) with chemotherapeutic agents, we demonstrated that low-frequency AC stimulation (ranging from 1 kHz to 5 MHz) significantly enhanced drug delivery and efficacy in resistant tumour cells. For instance, we observed a 50% increase in apoptosis and an 8-fold increase in cell death in drug-resistant medulloblastoma cells—remarkable outcomes that show promise in overcoming drug resistance.
Bioelectronics: A Game-Changer in Cancer Therapy
Our findings highlight the transformative potential of bioelectronics in cancer treatment. By facilitating the endosomal escape of GNPs, high-frequency AC not only improved drug delivery within the cell but also increased the sensitivity of these cancer cells to chemotherapy. Specifically, we found that this approach allowed GNPs to escape from endosomes, greatly enhancing the presence of chemotherapeutic agents in the cell and thus improving their efficacy.
Looking to the Future
The implications of these findings are significant. By merging electrical treatment with nanoparticle-based therapies, we are paving the way towards innovative, targeted treatments for some of the most aggressive and drug-resistant cancers. Our study showcases a new era in cancer therapeutics, where bioelectronic approaches can potentially be adapted to counter specific cellular mechanisms of drug resistance.
As we continue to develop and refine these techniques, we are increasingly confident in the potential of electromagnetic fields (EMF) for cancer treatment. We have now demonstrated multiple applications of EMF in treating cancer, including in our recent Nature Nanotechnology publication on wireless electrical signalling for targeted cancer cell apoptosis, and in our findings published in Bioelectronic Medicine, showcasing the versatility of bioelectronic therapies. Led by Dr Frankie Rawson, this body of work redefines our approach to cancer treatment and brings new hope in our quest to push the boundaries of what’s possible in combating these challenging diseases.
Interested in learning more? You can read the full publication study here.
References
Jain, A., Wade, P., Stolnik, S., Hume, A. N., Kerr, I. D., Coyle, B., & Rawson, F. (2024). Tackling Anticancer Drug Resistance and Endosomal Escape in Aggressive Brain Tumours Using Bioelectronics. ACS Omega. https://doi.org/10.1021/acsomega.4c05794
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