Multi-walled carbon nanotubes as a drug carrier for cisplatin in 2D monolayer and 3D spheroid breast cancer in vitro models

Hawley, Lucy (2024). Multi-walled carbon nanotubes as a drug carrier for cisplatin in 2D monolayer and 3D spheroid breast cancer in vitro models. University of Birmingham. M.Sc.

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Abstract

Current cancer therapeutics are limited by their lack of selectivity and specificity to cancer cells resulting in cytotoxic effects on bystander cells. Currently one of the most promising methods for drug delivery is the use of functionalised carbon nanotubes (CNTs). Their structure and surface properties allow for their excellent penetrative abilities into cells making them highly a prospective vector for the delivery of chemotherapeutic agents such as cisplatin (CDDP). In this work, we investigated Carboxylated Multi-Walled Carbon Nanotubes (MWCNT-COOHs) and their potential for the delivery of CDDP as a combination therapy. This study is highly novel as it is the first to assess the efficacy of these treatments by determining their cytotoxicity and effects on cellular metabolism in the MCF-7 breast cancer cell line using both 2D monolayers and 3D spheroid models.

MWCNT-COOHs demonstrated limited cytotoxicity to MCF-7 cells, even at high concentrations (up to 100μg/mL). They did, however, show some potential effects on MCF-7 cellular metabolism. The combination of CDDP with MWCNT-COOHs enhanced the effects of CDDP, resulting in greater cytotoxicity, inhibition of mitochondrial respiration and a metabolic shift to a more glycolytic phenotype and ATP production. This suggests that MWCNT-COOHs improve the delivery of CDDP into MCF-7 cells in both 2D monolayers and 3D tumour spheroid models. In conclusion, MWCNT-COOHs enhanced the efficacy of the chemotherapeutic agent CDDP while inflicting minimal damage themselves, suggesting that MWCNT-COOH : CDDP combinations could be a promising cancer therapy in future.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):