Core-Cross-linked Fluorescent Worm-Like Micelles for Glucose-Mediated Drug Delivery

We herein report the fabrication of core-crosslinked, fluorescent, and surface-functionalized worm-like block copolymer micelles as drug delivery vehicles. The polyether-based diblock terpolymer [allyl-poly(ethylene oxide)-block-poly(2-ethyl-hexyl glycidyl ether-co-furfuryl glycidyl ether)] was synthesized via anionic ring opening polymerization, and self-assembly in water as a selective solvent led to the formation of long filomicelles. Subsequent cross-linking was realized using hydrophobic bismaleimides as well as a designed fluorescent cross-linker for thermally induced Diels-Alder reactions with the furfuryl units incorporated in the hydrophobic block of the diblock terpolymer. As a fluorescent cross-linker, we synthesized and incorporated a cyanine 5-based bismaleimide in the cross-linking process, which can be used for fluorescence tracking of the particles. Furthermore, we covalently attached glucose to the allyl end groups present on the surface of the micelles to investigate active glucose-mediated transport into suitable cell lines. First studies in 2D as well as 3D cell culture models suggest a glucose-dependent uptake of the particles into cells despite their unusually large size compared to other nanoparticle systems used in drug delivery.

Automated summary

In this study, core-crosslinked, fluorescent, and surface-functionalized worm-like block copolymer micelles were fabricated for drug delivery. The micelles were synthesized through self-assembly and cross-linking, with fluorescent cross-linkers and glucose attached for fluorescence tracking and active glucose-mediated transport. Initial studies in cell culture models showed glucose-dependent uptake of the particles despite their large size compared to other nanoparticle systems.