Glycopolymers consisting of styrene (St) and pentafluorostyrene (PFS) were synthesized by a combination of nitroxide-mediated polymerization and "click" chemistry. A series of well-defined homopolymers as well as block and random copolymers of St and PFS were obtained with different ratios by using Bloc Builder as an alkoxyamine initiator. Some copolymers showed self-assembly behavior into regular nanospheres with diameters ranging from 70 to 720 nm by applying the nanoprecipitation technique. In addition, a thiol-glycoside (2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose) was reacted under ambient conditions with PFS moieties on the polymeric backbone utilizing a thiol-para fluoro "click" reaction. This nucleophilic substitution reaction was performed with high yields, and the reaction kinetic was monitored online with 19 F NMR spectroscopy. Finally, the deacetylation of the protected glucose moieties was carried out to yield well-defined glycopolymers. The polymers were characterized in detail by 1 H, 13 C, and 19 F NMR spectroscopy, size exclusion chromatography, and MALDI TOF-MS.

Fructose transporter GLUT5 is overexpressed in breast cancer cell lines, but not in healthy tissue. Micelles based on fructose, which were found to be low fouling, showed a high uptake by breast cancer cells (MCF-7 and MDA-MB-231 cells), but only negligible uptake by macrophages.

Many attempts have been made in the application of multicellular tumor spheroids (MCTS) as a 3D tumor model to investigate their biological responses upon introduction of polymeric micelles as nanocarriers for therapeutic applications. However, the micelle penetration pathways in MCTS are not yet known. In this study, micelles (uncrosslinked, UCM) were prepared by self-assembly of block copolymer poly(N-(2-hydroxypropyl) methacrylamide-co-methacrylic acid)-block-poly(methyl methacrylate) (P(HPMA-co-MAA)-b-PMMA). Subsequently, the shells were crosslinked to form relatively stable micelles (CKM). Both UCM and CKM penetrated deeper and delivered more doxorubicin (DOX) into MCTS than the diffusion of the free DOX. Additionally, CKM revealed higher delivery efficiency than UCM. The inhibition of caveolae-mediated endocytosis, by Filipin treatment, decreased the uptake and penetration of the micelles into MCTS. Treatment with Exo1, an exocytosis inhibitor, produced the same effect. Furthermore, movement of the micelles through the extracellular matrices (ECM), as modelled using collagen micro-spheroids, appeared to be limited to the peripheral layer of the collagen spheroids. Those results indicate that penetration of P(HPMA-co-MAA)-b-PMMA micelles depended more on transcellular transport than on diffusion through ECM between the cells. DOX-loaded CKM inhibited MCTS growth more than their UCM counterpart, due to possible cessation of endocytosis and exocytosis in the apoptotic peripheral cells, caused by faster release of DOX from UCM.

It is demonstrated that water-soluble, glucosylated poly(pentafluorostyrene) derivatives revealed favorable coating material properties for magnetic iron oxide nanoparticles. To prepare the coating material in high reproducibility and purity as well as in sufficient amounts, a new route of synthesis is established. The preparation and characterization of the glucosylated, tetrafluorostyryl monomer, by thiol-para-fluorine "click" reaction, and its polymerization, via nitroxide-mediated radical process, is presented in detail. In addition, the coating material and the resulting particle properties are investigated by means of XPS, DLS, TGA, TEM, and cryo-TEM as well as flow cytometry. The glycopolymer acts as an appropriate stabilizing agent for the superparamagnetic nanoparticles by the formation of an approximately 10 nm thick shell, as shown by the XPS analysis. Furthermore, the application of FITC-labeled glycopolymer yielded fluorescent, superparamagnetic nanoparticles, which can be used for monitoring cell-carbohydrate interactions, because these particles show no cytotoxicity toward 3T3 fibroblasts.

A new sugar-substituted 2-oxazoline monomer was prepared using the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. Its copolymerization with 2-ethyl-2-oxazoline as well as 2-(dec-9-enyl)-2-oxazoline, yielding well-defined copolymers with the possibility to tune the properties by thiol–ene “click” reactions, is described. Extensive solubility studies on the corresponding glycocopolymers demonstrated that the lower critical solution temperature behavior and pH-responsiveness of these copolymers can be adjusted in water and phosphate-buffered saline (PBS) depending on the choice of the thiol. By conjugation of 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranose and subsequent deprotection of the sugar moieties, the hydrophilicity of the copolymer could be increased significantly, allowing a cloud-point tuning in the physiological range. Furthermore, the binding capability of the glycosylated copoly(2-oxazoline) to concanavalin A was investigated.

Inspired by upregulated levels of fucosylated proteins on the surfaces of multiple types of cancer cells, micelles carrying β-l-fucose and β-d-glucose were prepared. A range of block copolymers were synthesized by reacting a mixture of 2-azidoethyl β-l-fucopyranoside (FucEtN3) and 2-azideoethyl β-d-glucopyranoside (GlcEtN3) with poly(propargyl methacrylate)-block-poly(n-butyl acrylate) (PPMA-b-PBA) using copper-catalyzed azide-alkyne cycloaddition (CuAAC). Five block copolymers were obtained ranging from 100 mol % fucose to 100% glucose functionalization. The resulting micelles had hydrodynamic diameters of around 30 nm. In this work, we show that fucosylated micelles reveal an increased uptake by pancreatic, lung, and ovarian carcinoma cell lines, whereas the uptake by the healthy cell lines (CHO) is negligible. This finding suggests that these micelles can be used for targeted drug delivery toward cancer cells.

An efficient and metal-catalyst free method of glycopolymer synthesis via thiol/para-fluorine "click" reaction was used to graft acetylated 1-thio-β-D-glucopyranose and 1-thio-β-D-galactopyranose onto a homopolymer of pentafluorostyrene (PFS) as well as onto a block copolymer of styrene and PFS. Subsequent deprotection of the carbohydrate moieties yielded well-defined, sugar-modified polymers (PDI < 1.2). The prepared polymers were not cytotoxic against 3T3 fibroblasts and MC3T3-E1 preosteoblasts. Furthermore, the water-insoluble copolymers were drop-cast and examined as synthetic biocompatible coatings on poly(propylene) substrates for culturing the investigated cell types. Both fibro- and preosteoblasts showed stable adhesion and proliferation on the glycopolymer-coated surfaces.

A well‐defined triblock terpolymer, poly(ethylene glycol)‐block‐poly(allyl glycidyl ether)‐block‐poly(tert‐butyl glycidyl ether) (PEG‐b‐PAGE‐b‐Pt‐BGE), with a narrow molar mass distribution has been synthesized by sequential living anionic ring‐opening polymerization. Afterward, the PAGE block was modified via thiol‐ene chemistry and different sugar moieties or cysteine as a model compound for peptides could be covalently attached to the polymer backbone. The solution self‐assembly of the obtained bis‐hydrophilic triblock terpolymers in aqueous media has been studied in detail by turbidimetry, dynamic light scattering, and transmission electron microscopy (TEM and cryo‐TEM). © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012