Dissertation
Polypept(o)ide-based Nanostructures for Therapeutic and Diagnostic Application
This doctoral thesis focuses on the development of polypept(o)ide-based nanostructures for therapeutic and diagnostic applications. The work combines controlled polymer synthesis, nanocarrier engineering, and biological evaluation to address current challenges in nanomedicine, with a particular focus on tuberculosis therapy and targeted radiotherapy.
- Author
- G. Schäfer
- Date
- 04 June 2026
- Links
- Thesis in Leiden Repository
Amphiphilic block copolypept(o)ides were synthesized and self-assembled into polymeric micelles for the delivery of hydrophobic anti-tuberculosis drugs. Stabilization through π-π interactions improved formulation stability, circulation time, and therapeutic efficacy in zebrafish and mouse models. In addition, multifunctional micelles co-encapsulating antibiotics and host-directed therapeutics were developed to enhance bacterial killing and host survival. Surface modification with mannose-based ligands was further explored to improve macrophage targeting and cellular uptake.
The thesis also presents PeptoBrush-based delivery systems for the sustained release of Auger radiotherapeutics for glioblastoma treatment. Finally, improved synthetic strategies for well-defined block copolypept(o)ides were established through optimization of polysarcosine-based macroinitiators and N-carboxyanhydride polymerization.
Overall, this work highlights the potential of polypept(o)ide-based nanocarriers as versatile platforms for advanced therapeutic and diagnostic applications.