Impact of Solvent on Crystal Structure of Nucleic Acid Encapsulated Polymorphic Zeolitic Imidazole Framework and Bioactivity

<p dir="ltr">Metal-organic frameworks (MOFs) are a group of porous materials formed through coordination chemistry. Their beneficial properties can be utilised in many different fields, including sensors and therapeutics. Their unique physicochemical properties make them attractive candidates for the delivery of therapeutic biomolecules. Their metal-ligand coordination disintegrates in acidic conditions, making them ideal candidates for the delivery of cancer therapy drugs. ZIF-8 is one of the most studied molecular objects capable of protecting drugs, enzymes, and nucleic acids. While some progress has been made in the field of MOF-based nucleic acid delivery, preliminary studies have only focused on the capability of MOFs as non-viral delivery vectors. </p><p dir="ltr">Phase transitions and polymorphism of ZIFs may have a significant impact on the behaviour of materials under varying conditions. Therefore, understanding the crystal phases of ZIF-8 is essential to tailor and control the physical, chemical, and mechanical properties of ZIF-8 for biomolecule encapsulation and delivery. For biomedical applications, it is crucial to find the best candidate for gene delivery with maximum therapeutic cargo and on-demand release potential. Finding a potential solution for cancer therapy has been an ongoing challenge for several decades. Therefore, materials sciences bring hope in making new candidates for cancer therapy. As cancerous cells possess unique physiological and biochemical properties, they can become resistant to traditional chemotherapy agents. The factors that influence the properties of ZIF agents and their ability to deliver nucleic acids to mammalian cancer cells are yet to be explored. </p><p dir="ltr">The principal aim of this thesis is to optimise methods for making phase-dependent ZIF biocomposites, to screen optimal phases for gene delivery and cellular uptake, to understand their stability and DNA encapsulation efficiency, to investigate the effects of solvents on phase transformation, and to develop methods to reduce the size of these biocomposites for retaining bioactivity and efficient delivery. The results of this project suggest that the mass fraction of precursors affects ZIF crystal topology, while washing solvent regulates the biocomposite crystal phase and stability. The interaction between ZIF biocomposites and serum protein is influenced by crystal topology, with porous sod ZIF showing greater interaction than non-porous carbonated ZIF-C. The project also explores the role of the tertiary amine in the biomimetic mineralisation of nucleic acid encapsulated ZIF, finding that low concentrations of amine reduce particle size and alter crystal phase while maintaining loading content integrity. Overall, these findings highlight the optimal ZIF phase for nucleic acid encapsulation and delivery, with potential benefit for gene therapy and biomedical applications.</p>