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Journal of Academic Research and Innovation

Abstract

Glioblastoma (GBM), categorised as Grade 4 IDH-wildtype, is a malignant and aggressive primary brain cancer in adults which exhibits persistent resistance to current therapies. Despite improvements in diagnosis and treatment, patient prognosis remains poor, with a median survival of 12-15 months. The significant inefficiencies of current treatments, such as surgery, chemotherapy, and radiation therapy, highlight the need for additional effective therapeutic strategies. The infiltrative nature of GBM helps with its aggression, proliferation and survival. Furthermore, a major issue in treatment is the presence of the blood-brain barrier (BBB), which acts as a blockade for many molecules entering the brain, including chemotherapeutic agents. Ultrasound (US)-mediated drug delivery has drawn increasing attention for the treatment of many cancers, with results showing increased cell cytotoxicity and uptake, particularly in GBM. In the treatment of brain cancer, these improvements are primarily due to optimised penetration of the BBB via the formation of membranous pores, which allows anti-cancer compounds to reach the brain more efficiently. This project aims to explore the potential of employing US in combination with different chemotherapeutic agents, such as Doxorubicin (DOX) and Temozolomide (TMZ), as a non-invasive treatment approach for human GBM, demonstrated on U-251 MG 2D-monolayer cell lines. The study’s findings highlighted the improvement of uptake and cytotoxicity in a dosage- and time-dependent manner in cells treated with DOX and US, in comparison to just DOX. Utilising US for DOX delivery resulted in a decrease in IC50 values, 24 hours and 6 days post-exposure and an 2 enhanced uptake. Due to concentration issues, TMZ only produced a maximal cytotoxic effect, negating any dose-response relationship. As a result, the primary focus of this project was oriented towards DOX. The findings from this study highlight the potential of US as an adjuvant therapy in the treatment of GBM, allowing for a more efficient delivery of chemotherapeutic agents, which may help overcome barriers associated with current therapeutic approaches.

Creative Commons License

Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

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