Synthesis of polymeric particles with biological recognition motifs for medical applications
Anwar, Naveed; Möller, Martin (Thesis advisor); Pich, Andrij (Thesis advisor)
Dissertation / PhD Thesis
Dissertation, RWTH Aachen University, 2017
The motivation for studying conjugated polymer particles (CPPs) comes from their reasonable photo- and physical and tunable fluorescence brightness. CPPs find applications usually in sensing, cell labelling, and long term imaging. However, use of CPPs in such applications is restricted due to high polydispersity of particles and inertness of CPPs surface. In this thesis, several facile methods of CPPs fabrication with narrow size distribution, characterization and functionalization of their surface with biological recognition motifs are described. We established a highly versatile method to fabricate extremely bright and light switchable CPPs. This approach can be easily applied to other switchable mono-mers provided they are dihalogenated to take part in the palladium-catalyzed cou-pling reactions. They can easily find applications in self-assembled switchable pho-tonics due to their fast switching characteristics, amorphous morphology and high monodispersity. The particles are attractive candidates for use in coatings, where they produce switchable physical color by diffraction or in photonic crystals for wavelength conversion with a switchable band gap or as colloidal laser resonators. We demonstrated a rise in fluorescence intensity together with the change in shape for switching from the trans-to-cis-conformation. All the particles could be used as switchable probes and markers for super resolution imaging in the biomedical field. In subsequent chapter, we demonstrated an easy approach to prepare monodis-perse CPPs using Sonogashira dispersion polymerization bearing acetylene moie-ties on the surface. These acetylene groups are functionalized with biological recognition motif using thiol-yne click chemistry. The particle size is tunable be-tween 140 nm and 300 nm. We applied the resulting functional particles as fluores-cent probes for imaging of endothelial cells, which take up the particles via receptor mediated endocytosis. To employ these particles in-vivo in future, we will develop near-IR emitters to allow excitation and fluorescence detection in the tissue trans-parency systems. We proved that the particles can bind to αVβ3 integrins on activat-ed endothelial cells under flow and static cell culture conditions showing potential of particles to be applied as non-bleaching near-infrared tumor probes and theranostic agents. In another study, we synthesized poly(ethylene glycol) (PEG) based microgels for the demonstration of glycans in a multivalent matter. Microgels with variable size, different functional moieties i.e. GlcNc, LacNAc, Galili and numerous concentrations of these glycans were prepared. These microgels can attach both lectin and lectin domain of TcdA due to specific interaction between them and glycans. We proved specific interactions between glycans and protein using FACS analysis. The micro-gels allow a facile diffusion of 124 kDa protein showing microgels mesh size is large enough. The system may be an ideal substitute for currently available antimicrobial therapy, as it deals directly with the inflammation causing toxin avoiding interruption of the intestinal flora. The versatility of the system can be seen by replacing glycans with different linkers and biomolecules. Altogether, this provides synthesis of highly selective microgels for various biological scavenging applications.
- DOI: 10.18154/RWTH-2017-06678
- RWTH PUBLICATIONS: RWTH-2017-06678