Molecularly Imprinted Nanoparticles for Diagnostic Applications

Molecularly imprinted polymers (MIP) are gaining increasing interest thanks to their low cost of manufacturing, robustness and stability compared to their bio-analogues such as antibodies. The molecular imprinting process can be defined as the generation of molecular recognition sites in a synthetic polymer. The template-derived sites thus created within the polymeric matrix allow MIPs (often referred as plastic antibodies, due to their synthetic nature) to selectively recognise and bind the target molecule. In light of these properties, MIPs have been successfully applied in sensors, assays and separation applications. Due to their small size, MIP nanoparticles (NPs or nanoMIPs) can be used in biomedicine, since the nanoscale format is potentially suitable for cellular or in vivo applications. The aim of this work is to demonstrate the suitability of the nanoMIPs as tools for imaging in cells. For this purpose, the choice of appropriate fluorescent moieties to be included in the nanoMIPs is crucial and depends on the intended application. Several fluorescent monomers were characterised and chosen as imaging functionalities to be employed in the synthesis of MIP NPs (Chapter 2). The innovative solid-phase approach used in this work enables the synthesis of nanoMIPs both in organics (for small templates) and in water (for peptides and proteins), with the possibility to tailor the particle’s surface chemistry according to the intended use. (Chapter 3 and 4). Only few examples of MIP NPs for cellular imaging have been reported so far. Such nanosystems should be biocompatible and physiochemically stable under physiological conditions, as demonstrated in Chapter 5 and 6. Thanks to their good biocompatibility and recognition properties, MIP NPs were successfully applied as membrane-targeted diagnostic tools (Chapter 7) in both cancer and senescent cells, thus paving the way for their in vivo use as diagnostic and imaging tools.