Synthesis and Characterisation of Metal Organic Frameworks for Use as Drug Delivery Systems in Neuroblastoma Therapy

Nduka, Izuchika Onyinyenna

Abstract

Gliotoxin, a secondary metabolite isolated from the fungi, Aspergillus fumigatus has
shown cytotoxic activity against neuroblastoma, a type of cancer accounting for 15%
of all childhood cancer-related deaths. But as with all other chemotherapeutic agents,
this compound is toxic to both tumour cells and healthy cells. To minimize toxicity
towards the healthy cells, a biocompatible drug carrier system is needed. For this
reason, this study has explored the use of metal organic frameworks (MOFs) – a class
of organic-inorganic hybrid materials made up of metal nodes held together by organic
bi or tridentate linkers – as drug delivery systems with the goal of achieving targeted
delivery of gliotoxin to neuroblastoma cells. Amongst the MOF systems investigated,
Cu-MOFs with RAWYAS and GIFKUC phases; and Fe-MOFs with MIL-100(Fe) phase
showed interesting results. The MOF systems were synthesized using microwaveassisted solvothermal/hydrothermal method, and their crystal structure, morphology,
porosity, and thermal stability studied by optical microscopy, scanning electron
microscopy (SEM), ultraviolet-visible spectroscopy (UV-Vis), Fourier transform
infrared spectroscopy (FT-IR) and x-ray diffraction (XRD). The amount of Gliotoxin
immobilized on the MOFs was determined by studying the kinetic of release using high
performance liquid chromatography (HPLC) for qualitative and quantitative analysis,
and the effect of the MOF-gliotoxin adducts on the cell viability of SHSY-5Y
neuroblastoma cell line and a non-cancerous cell line (CCD1070-Sk) was investigated
by means of MTT and Annexin V/PI assay. The result of the cell viability assays
suggests a synergism between the Cu-MOFs and gliotoxin as evidenced by the
enhanced cytotoxicity of gliotoxin and its selectivity for the tumour cells when loaded
on the MOFs. To rationalize this outcome, the nature of the intra-and inter-molecular
interactions between gliotoxin and the Cu-MOFs were explored by means of x-ray
photoelectron spectroscopy (XPS). The changes observed in the XPS spectra
suggests a strong co-ordination between the drug and the MOFs especially for the
GIFKUC phase. Overall, the findings of this study highlight an approach for enhancing
the pharmacological activity of gliotoxin by using MOFs as drug delivery systems.

Citation

Nduka, I. O. (2024). Synthesis and Characterisation of Metal Organic Frameworks for Use as Drug Delivery Systems in Neuroblastoma Therapy. (Thesis). University of Salford

• Thesis Type: Thesis
• Deposit Date: Mar 4, 2024
• Publicly Available Date: Mar 27, 2026
• Award Date: Mar 26, 2024