Real-Time evaluation of in vitro biocompatibility and drug delivery properties of Metal-Organic Framework nanocarriers

Markopoulou, Panagiota (2020) Real-Time evaluation of in vitro biocompatibility and drug delivery properties of Metal-Organic Framework nanocarriers. PhD thesis, University of Glasgow.

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Cancer is a major health issue and leading cause of death in modern society, hence great effort has been focused on developing drug delivery systems for use in targeted drug delivery. The use of nanoparticles offers numerous advantages. Among the newly developed systems, Metal-Organic Framework (MOF) materials pose excellent candidates. Being hybrid materials, they combine the advantages of purely organic and inorganic systems. Despite their advantageous properties, MOFs lack thorough and methodical evaluation of their biocompatibility. In this work, the in vitro biocompatibility of five MOFs is investigated. The materials were synthesised and characterised according to literature standards and their in vitro cytotoxicity was evaluated. Conventional end-point assays were evaluated for their appropriateness for use with MOF materials and real-time cell analysis was validated for the assessment of the in vitro overtime toxicity of MOFs, highlighting effects that would otherwise go undetected. In general, each material shown a unique profile suggesting that the observed cytotoxicity originates from the individual properties of each case. A good correlation between the toxicity of MOFs and their stability and metal leakage under simulated biological conditions was observed. Moreover, the internalisation pathways used for each material along with its overall internalisation efficiency were studied, showing material specific profiles. Finally, the overtime doxorubicin delivery from two types of MOF nanoparticles with different drug loading modes was evaluated. It was observed that, due to the different loading modes, the two drug carriers exhibited different mechanisms of drug delivery. In the case where doxorubicin was attached to the outer surface of the MOF, a gradual overtime cytotoxic effect was observed, while when doxorubicin was located inside the porosity a faster cytotoxic effect was observed. In general, this work not only offers an in-depth study on the biocompatibility, internalisation and drug delivery properties of MOFs, but also highlights the necessity of validation of the techniques used and investigation of their appropriateness for studying nanoparticulate systems. The importance of using multiple techniques in parallel in order to evaluate numerous parameters is highlighted throughout the entirety of this work.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Metal-Organic Frameworks, MOFs, nanoparticles, drug delivery, in vitro biocompatibility, real-time.
Subjects: Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Funder's Name: European Research Council (ERC)
Supervisor's Name: Forgan, Prof. Ross S.
Date of Award: 2020
Embargo Date: 1 June 2023
Depositing User: Panagiota Markopoulou
Unique ID: glathesis:2020-81390
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 28 May 2020 07:54
Last Modified: 28 May 2020 08:13

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