Theses (MSc. Medical and Health Sciences)

Metal-organic frameworks (MOFs) are hybrid crystalline porous materials comprising metal ions linked with organic building units via coordination bonds. Their high surface area, large porosity, and tunable structures make them ideal for medical, environmental, and industrial applications. However, MOFs are often synthesised using aromatic organic linkers derived from non-renewable petrochemicals, which are non-biodegradable and less biocompatible. Additionally, the common solvothermal synthesis method is time-consuming and yields lower output. To address these challenges, this study developed aliphatic zinc-based MOFs (ZnMOFs) using a microwave-assisted method. This approach significantly reduced reaction time while improving yield without compromising structural integrity. The ZnMOFs were characterised for their physicochemical properties, morphology, and thermal stability, demonstrating their suitability for biomedical applications. Doxorubicin (DOX), an anticancer agent, was loaded into the ZnMOFs to assess their drug delivery potential. The ZnMOFs achieved efficient drug encapsulation and exhibited controlled DOX release in acidic conditions (pH 5.6), mimicking the tumor microenvironment. Biological evaluations highlighted the biocompatibility and therapeutic potential of the ZnMOFs. Cytotoxicity assays revealed that ZnTDA MOF and ZnHDA MOF exhibited low toxicity towards both MCF-7 cancer cells (20-25% cytotoxicity) and HEK293 normal cells (IC50 = 1785-2374 μg/mL) while maintaining effective drug delivery with up to 40% cytotoxicity when loaded with DOX. In contrast, DOX-loaded ZnAdA MOF, DOX-loaded ZnDDA MOF, and DOX-loaded ZnAzA MOF even though showing lower cellular uptake but significantly higher cytotoxicity (up to 90%) against MCF-7 cells, suggesting a synergistic effect between the MOFs and DOX. These MOFs also demonstrated minimal toxicity towards HEK293 cells (IC50 = 117.4-1785 μg/mL), indicating their safety for normal cells. Overall, the synthesised aliphatic ZnMOFs via a microwave- assisted method are efficient, biocompatible, and effective in targeted cancer treatment. Their ability to encapsulate and release drugs in a controlled manner while reducing toxicity highlights their potential as safer alternatives to conventional MOF-based drug delivery systems.