Design and synthesis of iron oxide nanomaterials for biomedical applications

Baghdadi, Neazar Eassam

Chemistry
June 2016

Thesis or dissertation


Rights
© 2016 Neazar Eassam Baghdadi. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

Nanotechnology products have huge potential to be a part of the developments in various fields, including functional materials, electronics and medicine. Using nanomaterials in medical applications has been successful for disease diagnosis and drug delivery systems. One of the safest and most versatile nanomaterials utilized for medical purposes are iron oxide nanomaterials. This thesis presents the synthesis, coating and targeting vector modification of iron oxide materials for several biomedical applications including multimodal imaging and cancer cell targeting.

Iron oxide nanorods (NRDs) were produced and coated with silica shells as well as other surface modifying molecules including azamacrocycles (DO3A) and polyethylene glycol chains (PEG) which were attached in a one pot reaction. The presence of PEG on the NRDs surface gave improved suspension stability over a wide range of salt concentrations and pH values. Radiolabelling of the NRDs was demonstrated with the positron emitting radioisotope ⁶⁸Ga. The use of nanorods as magnetic resonance imaging (MRI) contrast agents gave a two-fold increase in T2 relaxivity (180 s⁻¹) compared to previous work using spherical nanoparticles.

The ⁶⁸Ga labelled NRD constructs show high radiochemical stability against transferrin challenge over a 3 h incubation period. An in vivo bio-distribution study was carried out by intravenously injecting a CD1 nude female mice with 2 mg of (NRDs-PEG), then multimodal imaging analysis was performed using MRI and positron emission tomography (PET) imaging. The NRDs with sizes between 100 to 200 nm showed rapid accumulation in the liver after 5 min due to uptake by macrophages and Kupffer cells as part of reticuloendothelial system, and a small quantity accumulated in the lung and spleen. It was also observed that in the MRI T2 weighted image, the liver is significantly darker than the T1 weighted imaging which confirms the sample accumulation. The multimodal images proved that the radiolabelled NRDs were stable in vivo on the timescale of
the imaging study.

Iron oxide nanoparticles (IONPs) were functionalised for targeting cancer cells. The IONPs were conjugated to a chemokine receptor targeting vector and the targeting properties were tested in vitro using Jurkat cancer cells with flow cytometry in an antibody competition assay. The NPs showed 100% inhibition of the anti-CXCR4 antibody binding in this assay.

Publisher
Department of Chemistry, The University of Hull
Supervisor
Archibald, Stephen J.
Qualification level
Doctoral
Qualification name
PhD
Language
English
Extent
4 MB
Identifier
hull:14799
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