- Doctoral Thesis
Rights / licenseIn Copyright - Non-Commercial Use Permitted
The work presented in this dissertation focuses on the design and development of novel, multifunctional and magnetic nanorobots for applications in the field of medicine. Minimally invasive and targeted biomedical procedures will greatly benefit from the progress made in nanotechnology. In this context, the doctoral work aims to address current medical challenges and presents novel therapeutic approaches, by combining the merits of nanotechnology, chemistry, and biology. Multiple integrated nanosystems of various shapes and material properties will be presented. Furthermore, multiple design strategies will be used to tailor nanoscale properties for the specific demands in the areas of antibacterial and cancer therapy. The first part of the dissertation will utilize the versatile fabrication technique of electrodeposition to fabricate magnetic nanorobots of different shapes (coils, tubes, wires) and demonstrate their potential for biomedical applications. Palladium (Pd) nanocoils were produced by electrodeposition, and subsequently coated with nickel (Ni) and silver (Ag) to render their magnetic and antibacterial properties, respectively. The magnetic manipulation and bacteria killing efficiency of the nanocoils was demonstrated for the treatment of Gram-negative Escherichia coli (E.coli) and Gram-positive methicillin-resistant Staphylococcus aureus (S. aureus), both of which belong to the leading multidrug-resistant bacterial pathogens. Next, magnetic Ni nanotubes were fabricated and used as a template for the design of a smart-multifunctional drug delivery nanoplatform. The high loading capacity of the inner tube cavity was utilized for the incorporation of a pH responsive chitosan (Chi) hydrogel, which enabled selective drug release in acidic environments (e.g. tumor area). The outer part of the nanomachines was coated with a gold (Au) layer to incorporate chemical conjugation sites. Here, the facile addition of biological markers, imaging agents, or drug molecules, by means of thiol-gold click chemistry, was demonstrated. Last, magnetic iron-palladium (FePd) nanowire alloys were designed and used for targeted bioorthogonal driven activation of a latent chemotherapeutic prodrug. The potential of the hybrid bioorthogonal nanocatalyst, as a novel, targeted anticancer therapy approach, was successfully demonstrated both in vitro and in vivo against a human breast cancer cell line. The second part of the dissertation will focus on advancements in the field of metal-organic frameworks (MOFs). First, a comprehensive biocompatibility study on the most prominent biomedical MOF - ZIF-8 - was conducted. The results suggested that ZIF-8 causes no cytotoxicity below a threshold of 30 µg/mL, whereas higher concentrations evoked DNA damage and subsequent cell death. Additional biomineralization studies with the therapeutic biomacromolecule insulin demonstrated that the therapeutic potential of ZIF-8 lies significantly below its cytotoxic threshold value. In the final part of this dissertation, the successful synthesis of a room temperature, ferromagnetic MOF structure was presented, for the first time. Magnetic characterization showed the tunability of the magnetic properties and its biomedical potential was highlighted as a novel gene delivery vehicle on human embryonic kidney cells. Show more
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ContributorsExaminer: Nelson, Bradley J.
Examiner: Pané i Vidal, Salvador
Examiner: Pêgo, Ana P.
Organisational unit03627 - Nelson, Bradley J. / Nelson, Bradley J.
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