Metal organic frameworks : from anticancer multifunctional drug delivery systems to novel vaccine adjuvants
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The research presented in this thesis aims to assess the capacity of metal organic frameworks for potential applications as drug delivery systems and novel vaccine adjuvants. The opening chapter (Chapter 1) provides a reader with a background to the field, metal organic frameworks synthesis routes and their potential applications in medicine and insight into the basics of immunology and biological assays as well as the anti-cancer drugs mechanisms and how it can be used to target the tumour cells. Chapter 3 describes the experimental techniques used in this research combining biological with chemical testing. Investigation of Zr-MOFs (UiO66 and UiO66-NH₂) and CPO – 27 (CPO Mg and CPO Ni) for their potential application as drug delivery systems for cisplatin is presented and compared in Chapter 4, as well as two different drug incorporation techniques (conjugation and physical encapsulation) in the case of UiO66-NH₂. The route proved to be more efficient when compared with encapsulation for the same MOF, and overall the most promising candidate for a drug delivery system for cisplatin, due to its large pores, was UiO66. Chapter 5 focuses on the potential application of Zr-MOFs and CPO-27 (Mg and Ni) as a drug delivery system for 5-Fluorouracil, a drug which because of its sparse solubility in water is challenging when it comes to its administration in the human body. Chapter 7 investigates the possibility to design multiple drug delivery systems utilising MOFs that contain cisplatin and fluorouracil in their framework, loading them with nitric oxide to increase the anti-cancer action and also to prevent thrombosis that may pose a danger to patients who undergo anti-cancer therapies. Chapter 6 describes the new concept of investigating MOFs (Zr-MOFs and Al-MOFs) as potential candidates as vaccine adjuvants. The research concluded that the performance of Al-MOFs, was better when compared to commercially available adjuvants.
Thesis, PhD Doctor of Philosophy
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