Synthesis of conjugated material systems for biological and medical imaging applications

Repenko, Tatjana; Pich, Andrij (Thesis advisor); Kühne, Alexander (Thesis advisor)

Aachen (2018, 2019)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2018

Abstract

Mankind is suffering from various types of diseases, which makes it imperative to improve diagnostics for early disease detection and adjust therapeutic strategies. Differentiation between benign and pathological tissue remains a major challenge especially in the early stages of disease and also during surgery in order to unambiguously diagnose and further achieve complete removal of pathological tissue and to minimize recurrence. In order to increase therapeutic efficiency and decrease side effects in treatment, the sensitivity and accuracy of diagnostic methods need to be improved. Biological- and medical imaging are essential technologies for These diagnostic purposes and the development of the associated imaging probes is imperative for highly specific localization and strong contrast. Disease profiles vary and lead to the necessity of patient stratification and tailored imaging probes precisely towards the requirements of individual patients. The resulting personalization Approach relies on availability of suitable imaging components, which can be customized to the application as preferred. The focus of this work is the development and synthesis of new biomedical-imaging probes. Conjugated organic materials are preferable because they exhibit exceptionally bright fluorescence due to their large π-conjugated system and delocalized electronic structure and additionally, their absorption and emission profiles can be easily tuned from the visible deep into the near infrared spectrum. Moreover, conjugated macromolecules and polymers have low cytotoxicity and are usually biocompatible. I will present different approaches how to generate bio imaging probes, which are functionalizable with biomedical recognition motifs and which are excretable either because they are small enough to pass the renal membrane or because they can be degraded. I will investigate their imaging capabilities, biocompatibility and targeting towards specific biomedical recognition motifs. More precisely, I will develop the preparation and characterization of: a) water-soluble biomimetic polymers, b) hybrid inorganic core/biomimetic polymer shell particles, c) bio-degradable highly fluorescent conjugated polymer particles and d) molecular water-soluble bio-functionalizable sonophores. The aim of the work is to develop a material toolbox for fluorescent and photoacoustic imaging, which can be applied and exchanged at will, depending on the type of diseased tissue and the site of use.