Modulating the cellular uptake of platinum drugs with glycopolymers

The therapeutic potency of platinum-based anticancer drugs can be substantially improved through the use of polymeric nanocarrier systems to target cancer cells efficiently. We synthesized a series of glyco-block copolymers with three different sugars able to self-assemble into nanoparticles when conjugated with 1,2-diamino-cyclopentane platinum(II) (DACP-Pt). The polymers are based on (2-(D-glucosyloxy)ethyl methacrylate (glucose; GlcMA), 2-(D-galactosyloxy)ethyl methacrylate (galactose; GalMA), 1-O-methacryloyl-β-D-fructopyranose (fructose; FrucMA1), and 3-O-methacryloyl-β-D-fructopyranose (fructose; FrucMA3)). They are all readily taken up intracellularly by the breast cancer cell lines MCF-7 and MDA-MB-231 and the ovarian cancer cell line A2780. All cell lines expressed a high preference for the fructose coated nanoparticles. The nanocarriers were themselves nontoxic, but exhibited high cytotoxicity and increased efficacy when conjugated with the DACP-Pt drug.