An efficient protocol for the synthesis of polymergemcitabine conjugates with variable composition and potential hepatoma-targeting property was achieved by combining selectively enzymatic transesterification with radical polymerization. Four polymerizable vinyl gemcitabine esters were first prepared by highly selective transesterification of gemcitabine with divinyl dicarboxylates using CAL-B as catalyst in acetone and characterized by IR, 1H-NMR, 13C-NMR, and ESI-MS. The effects of enzyme sources, organic solvents, and molar ratio of substrates on the enzymatic transesterification were investigated in detail. Then a,a'-azobis-(isobutyronitrile)-initiated homopolymerization of the resultant gemcitabine monomers was performed and three polymergemcitabine conjugates with high gemcitabine content (>55 wt %) were synthesized. Moreover, radical copolymerization of the gemcitabine monomer 5'-O-vinyladipyl-gemcitabine with different saccharide comonomers was performed, and three saccharide-functionalized polymergemcitabine conjugates with 5.715.3 wt % gemcitabine content were obtained, among which the conjugates with galactose or lactose as pendants had potential hepatoma-targeting function. All the resultant polymergemcitabine conjugates were characterized by IR, NMR, and gel permeation chromatography. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012