Inhaltszusammenfassung

Stimuli-responsive macromolecular drug delivery systems and smart nanomaterials from oligo- and polysaccharide block copolymers with amphiphilic character are emerging classes of compounds in nanomedicine. Combining a non-toxic character with controllable degradability, high biocompatibility and excellent solubility in aqueous solvents, they can serve as precisely tunable and robust nanomaterials and represent a green and sustainable alternative to artificial polymeric materials. With their i...Stimuli-responsive macromolecular drug delivery systems and smart nanomaterials from oligo- and polysaccharide block copolymers with amphiphilic character are emerging classes of compounds in nanomedicine. Combining a non-toxic character with controllable degradability, high biocompatibility and excellent solubility in aqueous solvents, they can serve as precisely tunable and robust nanomaterials and represent a green and sustainable alternative to artificial polymeric materials. With their inherent capacity to self-organize into micelles, rods or polymersomes they can protect and significantly improve the bioavailability of sensitive and pharmaceutically active cargo that would not be otherwise applicable in biological systems. This thesis reports several synthetic approaches towards end group functionalized dextrans and their application in the construction of amphiphilic responsive block copolymers and starlike polysaccharide brush architectures. Key steps of the synthesis include a versatile reductive amination by a modified microwave-assisted procedure, involving a co-solvent system, and the introduction of p-substituted aniline derivatives. Hereby it was possible to install useful functionalities at the chain end in an effective, facile and time saving manner. This approach led us to azide- and alkyne- end-modified dextrans, which were used for the Cu-promoted synthesis of the first-ever reported amphiphilic, pH-responsive block copolymer consisting solely of polysaccharide blocks. The material has surface-activity and self-assembles in water into spherical micellar nanoparticles. This Cu-mediated transformation was then further developed to a metal-free thiol-based approach. Hereby it was possible to gain access to single- and double-stimuli-responsive polysaccharide macrosurfactants from a single starting material. Their amphiphilic nature and degradation behavior were studied in detail with a focus on drug loading capacities and triggered release. A highly potent, near-infrared (NIR) absorbing photosensitizer was encapsulated and successfully delivered into the cytosol of HeLa cells, where a phototoxic effect was triggered with controlled NIR light exposure. The broad potential of end-on functionalized dextrans was then shown by developing dextran macromonomers for the ring-opening metathesis polymerization (ROMP) of polysaccharide brush polymers. Materials, that might become valuable intermediates in the synthesis of artificial proteoglycans for tissue engineering applications. In summary, with our established method we can synthesize biocompatible and responsive amphiphiles from sustainable resources by metal-free polysaccharide macromonomer ligation. More generalized, the synthetic procedure should be applicable to all polysaccharide systems with an inherent reducing end, giving access to a plethora of applications at the interface of biochemistry, polymer synthesis and material science (e.g. coatings, surfactants, surfmers, block copolymers and hydrogels).» weiterlesen» einklappen

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DDC Sachgruppe:
Chemie