Liver-targeting ribavirin-conjugating nanoparticles were successfully constructed via self-assembly of the lactose-functionalized amphiphilic random copolymer, which was facilely prepared by a two-step chemoenzymatic synthetic route. Aggregation morphology of the resulting self-assemblies observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) was regularly spherical shape, and hydrodynamic diameter determined by dynamic light scattering (DLS) was 174 +/- 27 nm. Critical aggregation concentration (CAC) was measured by fluorescence probe technology using pyrene as the hydrophobic molecule, and the CAC value was about 0.1 mg/L. Cell cytotoxicity tests performed by MTT assay showed that the nanoparticles had effective growth-inhibitory activity in hepG2 human hepatoma cells. Moreover, ribavirin could be slowly released from the copolymer with pseudo zero-order kinetics in different incubation media. The targeting nanoparticles self-assembled from amphiphilic random copolymers could be used as novel potential drug delivery vehicles. (C) 2008 Elsevier Ltd. All rights reserved.