Development of iohexol functionalized nanoparticles as contrast agents for medical computed tomography / Ammar Mohammed Alhasan

Ammar, Mohammed Alhasan (2023) Development of iohexol functionalized nanoparticles as contrast agents for medical computed tomography / Ammar Mohammed Alhasan. PhD thesis, Universiti Malaya.

	PDF (The Candidate's Agreement) Restricted to Repository staff only Download (249Kb)
	PDF (Thesis PhD) Download (2729Kb)

Abstract

Computed tomography (CT) is one of the most widely used methods for diagnosing diseases in human tissue, requiring contrast media to enhance images of different tissues and organs. However, the commercialized contrast media have several limitations, including short blood duration, requirement of high-concentration injection, and limited enhancement of specific tissues, nonspecific detection, and localization of the substance. Present studies have been carried out seeking to improve upon the contrast enhancement yield of commercially produced iodine (i.e. Iohexol). Building upon this motivation, present work has also emphasised the development of bi-modal (CT/fluorescence) contrast media for imaging diagnosis which offer complimentary and additional information beyond single mode imaging, having added benefits of high sensitivity, multicolour emissions, and low cost. Using the co-precipitation with drying preparation and nucleation doping techniques, the commercial Iohexol have been conjugated with hybrid silica-silver doped manganese oxide (Si-Ag:Mn3O4) and manganese doped zinc selenide (Mn:ZnSe), respectively. It is important to note that the process of synthesizing nanoparticles has been observed to generate different core sizes, influencing the characteristics of functionalised-nanoparticles and contrast yield enhancement. To seek support of this, the morphology, elemental composition, absorption and emission characteristics, as well as optical properties were analysed and evaluated, use being made of FESEM/EDX, HRTEM, TGA-DTG, FTIR, XRD, UV-visible and fluorescence spectroscopies. This was also followed by a preliminary study of the contrast enhancement in CT imaging. The crystallite size have been calculated using the Debye Scherer equation through benchmarking the main intensity of the diffraction peak at (121) iv and (101) with an average size of 53 and 17 nm for I@Si-Ag:Mn3O4 and I@MPA-Mn:ZnSe, respectively. It has also been obtained that the stability of fluorescence of I@Si-Ag:Mn3O4 is non-observable, while the I@MPA-Mn:ZnSe is appeared at 245 nm excitations with emission band centred at 585 nm. The contrast yield obtained from the CT Hounsfield Unit (HU) of I@Si-Ag:Mn3O4 and I@MPA-Mn:ZnSe nanoparticles increased linearly with increasing mass concentration, producing greater than 465 and 328 ΔHU over that of Iohexol, with a four-fold increment in HU at similar concentrations, respectively. In an extension to this, cytotoxicity studies have been conducted on the I@Si-Ag:Mn3O4 and I@MPA-Mn:ZnSe, confirming that the medium possesses good biocompatibility and low toxicity to cells CCD-18Co (CRL-1459™) and (HepG2 and MDA-MB-321) respectively. The results suggested that the synergy between the synthesized Si-Ag:Mn3O4 and MPA-Mn:ZnSe localized Iohexol on the surface have improved the performance of the contrast media, resulting CT enhancement and brightness of fluorescence, pointing to great potential of I@MPA-Mn:ZnSe in particular as a bi-modal contrast medium for further diagnosis applications.

Actions (For repository staff only : Login required)