Novel nanocomposites integrating Metal-Organic Frameworks (mofs) for biomedical engineering

Thesis

Metal-organic frameworks (MOFs) are fascinating hybrid materials, considered as promising nanocarriers for drug delivery. Their tailorability sets MOFs apart from their porous inorganic (zeolites and silica) and organic (carbon nanotubes) counterparts. To enable the use of MOFs for biomedical applications, new developments of sustainable MOF fabrication and characterization methodologies are sought. In this work, a detailed study the fundamental potential of MOFs as a ‘host’ to encapsulate various ‘guest’ drug molecules was carried out. Mechanochemistry and water-based approaches were systematically applied for the preparation of two model systems - the copper-based HKUST-1 and the iron (III) carboxylate MIL-100 (Fe), and theirvfeasibility for the fabrication of drug@MOF assemblies was demonstrated.

First, by leveraging two different mechanochemical approaches (i.e. manualvgrinding versus automated vortex grinding), the effects of different mechanochemical environments on the drug confinement were investigated. The outcomes were reflected in the release kinetics of 5-FU from the MIL-100 host, in which different guest–host interactions yielded from each technique led to variations in the release rate. Secondly, the mechanochemical preparation of drug-loaded MIL-100 (Fe) systems, comprising 5-FU, caffeine, or aspirin as guest molecules revealed the undocumented ‘modulator’ effect presented by 5-FU and caffeine. These molecules can be used to replace highly toxic mineralizers (e.g. hydrofluoric acid) in the preparation of crystalline MIL-100 (Fe). Thirdly, a novel water reconstruction process was developed to acquire highly crystalline MIL-100 (Fe). This approach was harnessed for the facile fabrication of the drug@MIL-100 systems, accomplishing up to ∼65 wt.% of drug cargo. Both strategies, mechanochemical and water-based synthesis, elucidated much-needed pathways towards an environmentally friendly and energy efficient preparation of MOF and guest@MOF systems, with improved cargo encapsulation capabilities.

New possibilities presented by high-resolution inelastic neutron scattering were brought to light for the characterization of drug-MOF interactions and structural changes arising from nanoscale confinement. Finally, this work presented the innovative application of synchrotron microspectroscopy to track the release of 5-FU molecules from a (5-FU@HKUST-1/PU) composite. Using experimental time resolved infrared spectra, jointly with newly developed density functional theory calculations, the detailed dynamics of vibrational motions underpinning the dissociation of 5-FU bound to the framework of HKUST-1 upon water exposure were revealed.

Overall, this work contextualizes future developments of MOFs as efficient drug delivery systems and expands the portfolio of synthetic and characterisation techniques applicable to the large realm of guest@MOF systems.

Authors: Souza, BE

• DOI: 10.5287/ora-zgaw6m24x
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Drug Delivery; Synchrotron microspectroscopy; Metal-Organic Frameworks; Inelastic Neutron Scattering; Mechanochemistry
• Subjects: Engineering; Green chemistry; Nanotechnology; Material Science; Mechanochemistry; Drug delivery