Core-Crosslinked Fluorescent Worm-Like Micelles for Glucose-Mediated Drug Delivery

Abstract

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-ethylhexyl 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.

Polyether‐Based Diblock Terpolymer Micelles with Pendant Anthracene Units—Light‐Induced Crosslinking and Limitations Regarding Reversibility

“…Pre-ordering of the diblock terpolymers in the thin polymer film may influence the resulting solution structure. [22,61] Crosslinking procedures for the micelles are described within the results and discussion section.…”

“…[19,20] Reversibility and adjustability can be achieved by, for example, using furan units as crosslinkable moieties and encapsulating a bismaleimide crosslinker beforehand. [21,22] Furan and maleimide units undergo Diels-Alder reactions at low to moderate temperatures which are thermally reversible. [23] In other systems, the formation of imines from amines and aldehydes [24] or hydrazones from hydrazines and aldehydes [25] present two types of linkages which can be created and cleaved upon changes in pH.…”

Breast tumor‐targeted drug delivery via polymer nanocarriers: Endogenous and exogenous strategies

“…While spherical shapes have prevailed, nonspherical carriers including rod-like, filament-like, and worm-like have also been studied. [31][32][33][34][35][36] Rod-like drug particles exhibited 100% tumor penetration if sized appropriately. 37 Filament-like micelles, also called filomicelles, showed longer blood circulation but weaker cellular uptake than spherical ones.…”

Weak Polyelectrolytes as Nanoarchitectonic Design Tools for Functional Materials: A Review of Recent Achievements

“…BCP-containing polyelectrolytes blocks have been used to design nanometer- to micrometer-sized vectors for use in drug delivery and encapsulation applications through manipulating the physicochemical properties of shells to adjust their permeability ( Figure 8 ) [ 220 ]. Stimuli such as pH and ionic strength changes create the opportunity to easily control drug-loaded vectors in open and closed states [ 221 , 222 , 223 ].…”