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Designed Polymer-Based Nanoparticles for Drug Delivery and Imaging
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Polymer chemistry has proven to be a very versatile technique for nanomedicine, as it allows the synthesis of nanoparticles with a wide range of architectures, sizes and surface chemistry. Most commonly, spherical nanoparticles have been employed. However, recent studies showed that the shape of nanoparticles also affects the bio-nano interactions.
The overall objective of this dissertation was to develop novel methods to synthesize polymer-based nanoparticles with enhanced properties for both drug delivery and diagnostics with an emphasis on shape. Furthermore, a dual-modality PET/MRI agent was developed to exploit the benefits of multimodal PET/MRI imaging and to enable high-resolution, high-sensitivity investigation of biological activity.
Firstly, in chapter 1, the current state of research in nanoparticles for drug delivery and imaging is discussed with a special focus on polymer-based nanoparticles and the importance of design.
In chapter 2, polymerisation-induced self-assembly was exploited to create a library of polymer-based nanoparticles with different sizes and shapes, and their efficacy as drug delivery vehicle was assessed to determine the optimal morphology. The results indicated that flexible worm-like nanoparticles have a higher tumour cell uptake and drug toxicity than spherical nanoparticles.
In chapter 3, a method was developed to synthesize novel epoxide surface-functional nanoparticles by polymerization-induced self-assembly, and the versatility of the functional group was investigated. In the second part of the chapter, the use of the different shaped nanoparticles as positive MRI contrast was investigated by successfully conjugating a gadolinium chelate onto the self-assembled nanoparticles. The worm-like nanoparticles showed a high MR contrast enhancement and have a great potential as imaging agent.
Finally, in chapter 4, a novel bimodal MRI/PET imaging probe was designed containing both gadolinium (for MRI) and radioiodine (for PET) by combining novel multicomponent chemistry with a core-cross-linked functional star polymer to optimally exploit the synergy between MRI and PET.