Modulating the cellular uptake of platinum drugs with glycopolymers
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The therapeutic potency of platinum-based anticancer drugs can be substantially improved through the use of polymeric nano-carrier 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-beta-D-fructopyranose (fructose; FrucMA1), and 3-Omethacryloyl-beta-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.