| Description |
Type 2 diabetes is a serious metabolic disorder characterized by insulin resistance and the gradual failure of pancreatic β-cells, leading to chronic hyperglycemia and the subsequent development of severe vascular, metabolic, and hormonal complications. Modern therapies employing GLP-1 agonists (e.g., liraglutide, semaglutide, or dulaglutide), which activate GLP-1 receptors on the surface of β-cells, significantly improve glycemic control. However, their efficacy is limited by a short circulation half-life, rapid proteolytic degradation, and suboptimal receptor interaction, necessitating frequent dosing. The aim of this project is to develop innovative conjugates of GLP-1 peptide agonists with biocompatible polymeric carriers that provide prolonged therapeutic action, enhanced stability, and more efficient interaction with GLP-1 receptors on target cells. The project also includes the integration of imaging-enabled structural motifs to allow monitoring of conjugate biodistribution and quantification of labeled β-cells using magnetic resonance or fluorescence-based techniques. Key emphasis will be placed on the rational design, synthesis, and detailed physicochemical characterization of water-soluble polymers based on phospho- and fluorinated polymer platforms, as well as their selective conjugation to GLP-1 agonists. The resulting conjugates will be evaluated in collaboration with domestic research partners (IKEM, FGÚ AV ČR) through both in vitro and in vivo studies, with the aim of monitoring pancreatic β-cell populations and assessing the conjugates’ ability to effectively stimulate insulin production. |
