Graphene oxide as a delivery system for oxaliplatin in 2D and 3D Tumour Models

Wang, Xiaoran (2023). Graphene oxide as a delivery system for oxaliplatin in 2D and 3D Tumour Models. University of Birmingham. M.Sc.

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Abstract

Graphene oxide (GO) has attracted a lot of attention in recent years as a novel drug delivery system due to its good stability and biocompatibility. However, the understand and research of GO ability to deliver anticancer drugs inside 2D monolayer cells as well as 3D tumour models need to be further. There is a gap in this field. For instance, the complexation of GO with platinum anticancer drugs is still under-investigated. In this study, the cell viability of oxaliplatin in 2D monolayer cells was assessed on colorectal (HCT116) and breast (MCF7) cancer cells at different seeding densities (5000 & 7000 cells per well) for 24 and 48hrs.

Next, we looked at the ability of graphene oxide (GO) to deliver the anticancer drug oxaliplatin. GO was prepared using the modified Hummer’s Methods and characterisation suggested the preparation of stable GO. The different concentrations of oxaliplatin were complexed with GO and assessed the cell viability on colorectal cancer cells (HCT116) and breast cancer cells (MCF7). The MTT and modified LDH assays were used to assess the cell viability of oxaliplatin alone and complexed with GO at different concentration and time points. It was found that GO complexed with oxaliplatin showed a dose-dependent trend on HCT116 cells after 48hrs but was not higher than oxaliplatin alone. In MCF7 cells, the combination therapy showed a higher reduction in cell viability especially at the highest concentration of oxaliplatin used for 48hrs.

Spheroids are an excellent 3D model to research the response of cancer cells to drugs and mimic the microenvironment of tumour in vitro. The establishment of an in vitro 3D cell culture model like spheroids will improve our understanding of the gap between two-dimensional cell culture and animal experiments. In this work, MCF7 based spheroids were prepared using the Liquid Overlay Method and then treated with GO alone, oxaliplatin alone and GO: oxaliplatin complexes to assess the ability of GO to deliver oxaliplatin inside the spheroids. After 48hrs and 72hrs following treatment of MCF7 spheroids with the combination therapy, a slight inhibition in the spheroid growth was observed which could be explained by the effective delivery of oxaliplatin inside the spheroids. In conclusion, GO could indeed become a potential drug delivery nanocarrier especially for platinum based anticancer drugs.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):