Design and synthesis of metal organic frameworks for encapsulation of multiple anti-cancer drugs and environmental applications

Metal-Organic Frameworks (MOFs) have the potential to offset some of the terrible side effects caused by the drugs currently used in cancer treatment. MOFs have high porosity, low cytotoxicity, good biocompatibility, biodegradability, and target-specific behaviour, encapsulating drugs and subsequently releasing them at tumour sites. MOFs allow for a slower release of the drugs, preventing the burst effect caused by immediate release of the drug. Although the potential of MOFs as drug carriers has been well established, their use in combinatorial treatments that involve more than one drugs has been less investigated. Dual drug encapsulation and release would improve the potency of the anti-cancer treatment because of the synergistic effect of the two drugs. Dual drug encapsulation and release can also help to overcome the multidrug resistance effect that comes from cancer cells becoming resistant to anti-cancer drugs. With the above in mind, we decided to explore the potential of MOFs as multiple drug carriers. For this purpose, NUIG4 was used, it holds the record in doxorubicin (DOX) uptake, it is water stable and biocompatible and protects the healthy cells from the drug cytotoxicity. Herein, the capacity of NUIG4 to deliver dox or mitoxantrone (MIT) and 5-fluorouracil (5-FU) is reported. Each anti-cancer drug that are used in this project have a different mechanism of action; this can help to overcome multidrug resistance. 5-fluorouracil intercepts the replication of the cancer cells genetic material, due to the cancer cells mistaking 5-fluorouracil for uracil, while doxorubicin hydrochloride intercepts the replication process of the cancer cells by DNA intercalation, it slots itself between the base pairs of DNA. Mitoxantrone is a synthetic anti-cancer drug which is similar in structure to anthracycline drugs, such as doxorubicin. It has a similar mechanism of action to that of doxorubicin. The initial results suggest the successful encapsulation of DOX/ MIT and 5-FU, and a controlled release of the drugs, as a result of the large pore size and subsequent large internal surface area. MOFs also have the potential to encapsulate different environmentally toxic materials. This thesis reports the capacity of NUIG4 to encapsulate Tetracycline hydrochloride (TET). TET is an antibacterial drug which is used for the treatment of animals and humans. It is dangerous for the environment; it damages microbial communities and inhibits algae growth. It is often slow to degrade and infiltrates water systems, which can increase antibiotic resistance. The removal of TET from the environment would lower antibiotic resistance and allow algae growth, preliminary results show the successful encapsulation of TET by NUIG4. The large pore size and internal surface area of NUIG4 allow for this encapsulation. The synthesis of novel MOFs is very important as it can result in MOFs which can encapsulate more complex compounds, or it could result in new synthesis methods of MOFs. These new synthesis methods could be more environmentally friendly MOFs, though they are still capable of encapsulating a wide variety of guest molecules for many different applications. The final project covered in this thesis shows the synthesis of a novel MOF synthesised by the mechanochemical synthesis method. This method involves physical force causing chemical reactions, it is solvent free and has a high yield. It had successful encapsulation of an anti-cancer drug.

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University of Galway

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Attribution-NonCommercial-NoDerivatives 4.0 International

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University of Galway Theses (Research Masters Theses)