Polymers are widely investigated as carrier system for drugs in order to maintain the concentration of the drug in the body within a therapeutic window while avoiding frequent drug administrations.
Glycopolymers, synthetic polymers carrying pendant sugar units, have been shown to target carbohydrate receptors on cancer cells. They have attracted extensive attention in the fields of polymer chemistry, material science and biomedicine due to their properties, which include biocompatibility and bioactivity. Particles consisting of self-assembled, amphiphilic, galactosylated block glycopolymers revealed an enhanced uptake by human hepatocellular carcinoma cell line (HepG2), as compared to the water-soluble homopolymers.
In this work, since platinum drugs are highly efficient in the treatment of cancer despite of their adverse side effects, a range of triblock copolymers have been studied with three different sugars able to self-assemble into nanoparticles when conjugated with cis-platin (cis-Pt).
Trimethylsilyl-protected propargyl methacrylate (TMSpMA) monomer was polymerized in the presence of a furan protected maleimide functionalized 4-cyanopentanoic acid dithiobenzoate (CPADB-MI). P(TMSpMA) Macro-RAFT agent was then chain extented with the monomer of 1,1-Di-tert-butyl 3-(2-(Methacryloyloxy)ethyl)-butane-1,1,3-tricarboxylate (MAETC). Following this polymerization, γ-Benzyl-L-glutamate N-carboxyanhydride was polymerizaized by using the ring-opening polymerization to obtain poly(β-benzyl L-glutamate) (PBLG) and PBLG was coupled with P(TMSpMA-b-MAETC) via click reaction to give corresponding triblok glycopeptide polymer. After deprotection of trimethylsilyl units, a range of glucosylated triblock copolymer were synthesized by reacting a mixture of 2-azideoethyl β-D-glucopyranoside (GlcEtN3), 2-azideoethyl β-D-mannopyranoside (ManEtN3) and 2-azidoethyl β-L-fucopyranoside (FucEtN3) with P(PMA-b-MAETC-b-PLBG) using copper-catalyzed azide−alkyne cycloaddition (CuAAC). The resulting polymer was used as a macromolecular ligand for the conjugation with platinum drug. Thermogravimetric analysis showed full conjugation. The resulting drug loaded nanoparticles had hydrodynamic diameters of around 100 nm. For chacterization of organic synthesis and polymerizations 1H-NMR, 13C-NMR, FT-IR and GPC analysis are succesfully done.
