- Title
- The development of palladium nanoparticles for radiopharmaceutical application
- Creator
- Gandidzanwa, Sendibitiyosi
- Subject
- Nanotechnology
- Subject
- Nanostructures Nanofluids
- Date Issued
- 2019
- Date
- 2019
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- http://hdl.handle.net/10948/42163
- Identifier
- vital:36631
- Description
- The dissertation describes an in-depth synthesis and optimisation of palladium(0) nanoparticles of three distinct size ranges, respective capping agents, and cellular uptake studies using a non-toxic concentration (10 μM), laying a foundation for the design of palladium-based folate receptor-targeted theranostic nanoradiopharmaceutical. In the preliminary selection to determine the optimal diamines for the study, ethylenediamine, hexamethylenediamine, 1,10-diaminodecane, 1,12-diaminododecane, 1,4- diaminobenzene, 4,4’-ethylenedianiline, 1,2-diphenyl-1,2-diaminoethane, and tetraaminophthalocyanine were employed. The characterisation of the nanoparticles obtained from the in situ reduction of palladium(II) salt at room temperature by either 1,2,3- trihydroxybenze (pyrogallol), citric acid, sodium metabisulphite, sodium borohydride, hydrazine hydrate, or formaldehyde was performed. Ethylenediamine and sodium borohydride were found to be the best diamine capping and reducing agent, respectively. Systematic investigations determined that the nanoparticle synthesis was dependent on various reaction parameters: such as reaction temperature, time, reductant reducing power, and capping agents. The parameters effects on the nanoparticle size, morphology, shape, stability, crystallinity, and surface charge were investigated. The optical properties, elemental composition, functional group, concentration and molecular weight for the synthesised nanoparticles or conjugates were determined. These properties were analysed using Ultraviolet–visible spectroscopy (UV-Vis), high resolution transmission electron microscopy (HRTEM) coupled with selective area electron diffraction (SAED) and energy dispersive X-ray spectroscopy (EDS), X-ray powder diffraction (XRD), zeta potential (ZP), dynamic light scattering (DLS), elemental analysis (EA), 1H and 13C-nuclear magnetic resonance (1H- and 13CNMR), Fourier-transform infrared spectroscopy (FTIR), inductively coupled plasma-optical emission spectroscopy (ICP-OES), and liquid chromatography-mass spectroscopy (LC-MS). The in vitro cytotoxicity, cell uptake, and internalisation studies of palladium nanoparticles (10 μM) ranging in size and different types of capping agent were performed using three breast cancer cell lines: MDA-MB-468 , MCF-7 and MDA-MB-231 , and a non-tumorigenic MCF-10A breast cell line. The cell uptake and internalisation were investigated using ICP-OES and TEM. A high dependence between reduction rate and concentration of palladium precursor was observed for the room temperature synthesis of palladium nanoparticles, and the employed synthesis procedure will be applied to the hot palladium isotope (109Pd). A facile, green, aqueous synthesis route for palladium nanoparticles at room temperature was developed, and the synthesised nanoparticles indicated narrow size distributions. A concentration dependence between cytotoxicity and palladium nanoparticles was observed, with lower concentrations (10 μM) exhibiting minimal cytotoxicity relative to higher concentrations (100 μM). The cellular uptake of palladium nanoparticles was found to be concentration, folate-receptor, capping agent, and cell line proliferation-dependent. Well-defined, monodispersed, and negatively charged folate-ethylenediamine and folate-phthalocyanine capped palladium nanoparticles were taken up by cells, with higher nanoparticle internalisation in folate receptor positive tumorigenic cells relative to folate receptor negative non-tumorigenic cells. It can be concluded that palladium(0) nanoparticles can be synthesised from the reduction of palladium(II) by sodium borohydride at room temperature. The folate-conjugated palladium nanoparticles are non-cytotoxic at 10 μM and were successfully optimised and selectively delivered to folate receptor-positive breast cancer cells (MDA-MB-231 and MCF-7) relative to non-tumorigenic breast cells (MCF-10A) and folate receptor negative cancer cells (MDA-MB-468).
- Format
- xxxvi, 180 leaves
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
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NMU School of BioMolecular and Chemical Sciences
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Sendibitiyosi Gandidzanwa.pdf | 11 MB | Adobe Acrobat PDF | View Details Download |