Universität zu Köln

Mattern, Annabelle ORCID: 0000-0002-2512-2165 (2021). Investigations Towards Biofunctionalised and 99mTc Radiolabelled Gold Nanoparticles. PhD thesis, Universität zu Köln.

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Abstract

This work concentrates on the synthesis and functionalisation of monodisperse gold nanoparticles within a size range of 5 to 30 nm. These were further functionalised with either biogenic substances such as carbachol, adrenaline or atropine or with a biomimetic compound like dihydrocaffeic acid. Different synthetic routes are described, and state-of-the-art analyses such as transition electron microscopy, multidimensional heteronuclear magnetic resonance, dynamic light scattering, optical absorption spectroscopy, high performance liquid chromatography and mass spectrometry are presented throughout and confirm the size of the nanoparticles and their successful functionalisation. Furthermore, this thesis discusses the physiological studies of the biofunctionalised gold nanoparticles, which showed biological activity and even multivalent stimulation of various receptor types in different biological systems including intestinal, cardiac and respiratory tissues. This work demonstrates that the application of biofunctionalised gold nanoparticles can surpass the biological effects of the free parent compound by several orders of magnitude. Further prospective functionalisations are presented, such as the labelling of gold nanoparticles with fluorescent dyes, including the necessary modifications of the fluorophore. As the biodistribution of gold nanoparticles within the whole body is of great interest, this thesis focusses strongly on investigations towards gold nanoparticles radiolabelled with 99mTc. Using a mono ligand shell (only carrying chelating ligands) or a mixed ligand shell (carrying chelating ligands as well as a biogenic substance), these radiolabelled functionalised gold nanoparticles could potentially function as probes for imaging investigations and be subject to future studies towards radiotheragnostics. In particular, this thesis presents how the tridentate chelating ligand picolylamine diacetic acid (PADA) was used showing promising results regarding the complexation of 99mTc and its heavier group 7 homologue Re. Connecting PADA with a mercaptoalkyl linker enables the ligand to attach to the gold nanoparticle surface with the thiol group. Furthermore, a spacer with a longer alkyl chain ensures the required stability of the functionalised gold nanoparticles. The radiolabelling procedures were performed under mild conditions and in a time efficient manner, as 99mTc only has a half-life of 6 h. Special emphasis was placed on the purification and the analytical characterisation of the radiolabelled gold nanoparticles, which were obtained as stable pink dispersions and which were directly analysed by size exclusion chromatography with a γ detector. Post-labelling analyses were also carried out and confirmed the integrity of the material.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Mattern, Annabelle annabelle.mattern@uni-koeln.de orcid.org/0000-0002-2512-2165 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-538363
Date:	2021
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Inorganic Chemistry
Subjects:	Chemistry and allied sciences
Uncontrolled Keywords:	Keywords Language Gold English Nanoparticle English Technetium English Biofunctionalisation English Radiolabelling English Monodisperse English
Date of oral exam:	25 October 2021
Referee:	Name Academic Title Wickleder, Mathias S. Prof. Dr. Grüll, Holger Prof. Dr. Alberto, Roger Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/53836