Conjugated Polymer Nanoparticles for Near Infrared Fluorescence Imaging

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In this work we will produce a fluorescent nanoparticle system for high performance clinical near infrared (NIR) in vivo imaging, an extremely promising technology that is currently being held back by the use of poorly performing organic dyes as fluorescent imaging agents.NIR light, at wavelengths between 700 and 1000 nm, exhibits high tissue penetration and can therefore be used to non-invasively visualise structures inside the body. High performance NIR in vivo imaging has long been mooted as a highly promising alternative to nuclear imaging techniques, as it exhibits improved sensitivity and resolution, as well the obvious benefit of replacing the use of the radioactive tracer materials which pose a risk to both patients and clinicians. Although NIR imaging will be useful for a variety of diagnostic applications, it is currently considered to be particularly promising for imaging of the lymphatic system, specifically in relation to its role in cancer metastasis. NIR imaging is not currently used in the clinical setting due to a lack of strong and stable NIR contrast agents. Small molecule organic dyes are commercially available and have been investigated as NIR contrast agents, but their weak fluorescence emission limits their practical use. Development, approval and commercialization of NIR imaging agents with enhanced performance over organic dyes will be a vital step towards maximising the potential of NIR in vivo imaging.In the work proposed herein, nanoparticles will be synthesised from conjugated polymers which exhibit extremely strong absorption and fluorescence emission. Conjugated polymer nanoparticles (CPNs) have emerged as highly promising fluorescent probes for in vivo imaging as they exhibit excellent optical properties whilst lacking the intrinsically toxic ingredients found in other fluorescent nanoparticles such as quantum dots (cadmium, for example). NIR fluorescence will be achieved by combining CPNs with NIR-dyes to create a system which couples high energy absorption with efficient energy transfer to produce strong NIR fluorescence brightness. The key feature of these nanoparticles is that both their excitation and emission maxima will be in the NIR - an absolute prerequisite for NIR in vivo imaging, and a functionality that has not been achieved in CPNs to date. A second defining feature of our strategy to develop CPNs as NIR imaging agents is the incorporation of extensive in vitro and preliminary in vivo safety testing as an intrinsic part of the nanoparticle design phase (i.e. Safety-by-Design). This forward-thinking approach will ensure that a clinically viable system is chosen for investigation from the start, thus promoting maximum efficiency of project time and funding. The programme to generate and optimise a high performance, safe NIR-emitting nanoparticle system will be completed in three phases: 1) Systematic investigation of nanoparticle properties (optical, physicochemical and in vitro safety) from selected combinations of conjugated polymers and NIR dyes; 2) Selection of one nanoparticle system for subsequent optimization and comprehensive in vitro safety testing; 3) in vivo performance evaluation and preliminary in vivo safety testing. This project is extremely timely as global interest in CPNs is increasing rapidly. The KCL investigators have been at the forefront of this exciting area of research over the last five years, and have already made a significant contribution by being one of the first groups internationally to produce conjugated polymer nanoparticles and transfer them into biomedical applications. The further expansion of this work towards clinical applications in NIR imaging will strengthen the UK lead in the rapidly evolving sector of medical engineering.