Redox-responsive biodegradable polymeric materials for biomedical applications

Abstract

In recent years, biodegradable and stimuli-responsive polymeric materials have gained importance in cancer research and biomedical applications. Such materials can be used as implants in the body and a nano-sized drug delivery system. Within the scope of this thesis, three different stimulus- sensitive biodegradable polymer dendron conjugate systems were prepared, and micellar nanostructures were obtained with these structures. The hydrophobic drug was physically loaded into the micelle structures in the first three projects. In the first and second projects, a targeting group was used to increase the efficiency of the drug delivery system. These micellar carriers make the hydrophobic drug water-soluble in body fluid and use both passive and active targeting pathways to ensure that the drug is collected in tumor tissues. The size of micellar structures was appropriate in all three projects when examined in terms of their suitability for delivery based on the enhanced permeability and retention (EPR) effect. The first two projects used cyclic RGDfK as the targeting group. It was observed that the drugs incorporated into the micellar nanostructures with the targeting group accumulated more effectively in the breast cancer cells. Doxorubicin was used as a chemotherapy agent. The last study synthesized cryogels containing varying amounts of a thiol- reactive monomer. Facile and reversible functionalization of cryogels were demonstrated through the attachment of a fluorescent dye (Bodipy-SH) and bioactive ligands such as biotin-thiol and mannose-thiol to recognize Streptavidin and Concanavalin-A, respectively. The proteins bound to the cryogels were amenable to release through treatment with a thiol-containing reducing agent such as dithiothreitol (DTT). Overall, the novel thiol reactive macroporous cryogel structures will be a fascinating platform for various biomedical applications where a catch and release approach of analytes is necessary.