Abstract
Semiconducting polymer nanospheres are organic conjugated polymer nanoparticles which are synthesized from benign materials and exhibit excellent fluorescence properties. The nanoparticles are generally larger than inorganic quantum dots with a relatively broad size distribution. Quantum dots, on the other hand, which have extensively been developed and synthesized with precise and narrow distributions of a few nanometers in dimensions, are now being widely investigated as bio-imaging agents, despite the rising concerns about their toxic compositions. Therefore, advances in the synthesis of the organic nanoparticles and investigations into their suitability as alternatives to quantum dots need to be explored.The ‘size problem’ of semiconducting polymer nanospheres – polymer particles are significantly larger than quantum dots – was first tackled in this work. With modifications to the miniemulsion-evaporation synthesis method, narrowly distributed quantum dot-sized nanoparticles with diameters as small as 2 nm were synthesized. These organic nanoparticles which were capped/entwined with poly(ethylene) glycol (PEG), a Food and Drug Administration (FDA) approved surfactant, were found to conserve most of the optical properties of their constituent polymers, and are therefore expected to be useful in bio-imaging applications similar to their larger counterparts.
A second nanoparticle system with a dual-modality was then prepared; semiconducting polymer nanospheres capped/entwined with three amphiphilic lipids one of which was gadolinium – diethylene triamine pentacetate, a Magnetic Resonance Imaging (MRI) active ligand. These bimodal nanoparticles also maintained their optical properties, were readily taken up by two cell lines, were distinguishable from the auto-fluorescence of animal tissue, and were found to be MRI-active as revealed by their MRI relaxivity measurements.
Finally, the optimized organic nanoparticles and similarly coated quantum dots were investigated for their potential to interact with human blood components, a physiological system which may be very relevant for semiconducting polymer nanospheres used as medical diagnostic agents. The preliminary ex-vivo studies performed revealed that similarly coated organic nanoparticles and quantum dots did not induce platelet aggregation or alter aggregation behaviour in response to a physiological agonist. Further, no evidence of platelet activation, neutrophil activation or increases in platelet-monocyte adhesion was observed. This implied that introduction of the nanoparticles to the blood stream at the concentrations tested may not elicit acute pro-inflammatory effects or alter normal coagulation pathways, although further rigorous evaluation in this area is still required. Fluorescence imaging showed that the organic nanoparticles were taken up by different blood cells and also showed some evidence of adhesion to their surfaces, a property which might find an application in the future. Ultimately, more short-term and long-term safety studies (in-vitro, ex-vitro, and in-vivo) must be conducted before deriving any further conclusions.
| Date of Award | 1 Oct 2013 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Mark Green (Supervisor), David Richards (Supervisor), Lea Ann Dailey (Supervisor) & Philip Blower (Supervisor) |