Polymer coated iron oxide nanoparticles for intracellular tracking and diagnostic applications

Elhuni, Ibteisam (2019) Polymer coated iron oxide nanoparticles for intracellular tracking and diagnostic applications. PhD thesis, University of Nottingham.

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Abstract

Engineering iron oxide nanoparticles (IONPs) is essential to enhance their efficiency and specificity for biomedical applications such as MRI contrast enhancement, cellular therapy such as cell labelling and cell targeting. IONPs were prepared by a co-precipitation method and coated with various polymers poly(Glycerol Adipate) (PGA 40%C18), Poly(Ethylene Glycol) - poly(Glycerol Adipate)-Succinic Acid (PEG-PGA-SA) and Poly(Ethylene Glycol) - poly(Glycerol Adipate) 40%C18 (PEGylated PGA 40%C18). From the three different coated IONP preparations, only PEGylated PGA 40%C18 demonstrated the ability to produce small-coated particle sizes. The size, shape and surface charge of uncoated and coated IONPs were characterised using dynamic light scattering (DLS), transmission electron microscopy (TEM) and zeta-potential. The sizes of IONPs after coating were 22, 50, 80 nm respectively, and the results of zeta potential measurement indicated that the surface charge of uncoated nanoparticles changed from positive to negative after coating with polymer. PEGylated PGA 40%C18 coated iron oxide nanoparticles showed high stability against aggregation under physiological conditions. Rhodamine B isothiocyanate was incorporated into the polymer layer and used as a fluorescent marker.

The effect of PEGylated PGA 40%C18 coated IONP of various sizes on the uptake by a respiratory epithelial cell line (Calu-3) was investigated. The internalisation mechanism and intracellular localisation was determined using a range of advanced imaging techniques including confocal microscopy and transmission electron microscopy (TEM). The results suggested that for PEGylated PGA 40%C18 coated IONPs there was a clear correlation between particle size and cellular uptake. Uptake was particularly high for nanoparticles with size 22 nm. Quantitative determination of cellular iron uptake performed by colorimetric ferrozine assay was in agreement with confocal microscopy results. The permeability coefficient (Papp) was used to determine the permeability of 22 nm coated IONP, but the larger particles showed a negligible permeability. Mechanism of nanoparticle cellular uptake was mainly by direct diffusion through the cell membrane for all IONP sizes. However, some particle uptake for the larger IONP (50 and 80 nm) was by the expected vesicular route, and this was probably seen due to the slower diffusion of these IONP through the membranes.

The MRI contrast of IONPs coated with a thin layer of PEGylated PGA 40%C18 was evaluated with1.5T Philips Achieva MRI scanner through measurement of their relaxivities. Polymer coated IONPs of size 50 nm have a good r2 relaxivity value but the other sizes were inferior. The MRI results highlight an opportunity for further optimisation of the core/shell ratio of IONPs, which could enhance relaxivity effects for their medical applications as contrast agents in the near future.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Garnett, Martin
Stolnik-Trenkic, Snow
Keywords: iron oxide nanoparticles; biomedicine; nanotechnology
Subjects: R Medicine > RS Pharmacy and materia medica
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 55921
Depositing User: Elhuni, Ibteisam
Date Deposited: 04 Sep 2019 10:23
Last Modified: 07 May 2020 08:30
URI: http://eprints.nottingham.ac.uk/id/eprint/55921

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