Multivalent targeting of GLUT5-transporters through wormlike micelles with controlled size, stability, and ligand density

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The aim of this project is the preparation of wormlike micelles with controlled length, stability, and composition for selective uptake into breast cancer cells via multivalent targeting. This is realized through the synthesis of amphiphilic polyether- and polyester-based block copolymers with varying weight fractions and crosslinkable units in the side chain of the hydrophobic segment. Further, differently functionalized derivatives of 2,5-anhydromannitol (AMtl) will be synthesized and covalently attached to the hydrophilic block using suitable conjugation reactions. AMtl features a high affinity to a fructose-selective transporter, GLUT5, which is known to be overexpressed in many breast cancer cell lines. Subsequent co-assembly strategies using different block copolymer mixtures with varying content of AMtl-units allow then the preparation of wormlike micelles with controllable density of AMtl within the micellar corona. Depending on length and flexibility of such nanostructures, several GLUT5-receptors on the surface of such cells can now be addressed simultaneously. In that way, we aim at a higher specificity of wormlike micelles if compared to spherical analogues with regard to the targeted breast cancer cell lines. Within the framework of this project, we will also investigate the influence of micellar stability (e.g., mediated using core crosslinking) on cell uptake via endocytosis under static and dynamic conditions. As an alternative to core-crosslinking, we will also employ hydrolytically sensitive polyester blocks as core-forming segments.