Fabrication of novel hepatoma-targeting microdisks by hydrogen bond-assisted self-assembly of an azacitidine-conjugating amphiphilic random copolymer

Novel hepatoma-targeting azacitidine-conjugating microdisks were successfully fabricated by hydrogen bond-assisted self-assembly of an amphiphilic random copolymer with galactose and azacitidine as pendants, poly(5′-O-vinyladipyl-azacitidine-co-6-O-vinylsebacyl-galactose). The random copolymer was easily prepared by a two-step chemoenzymatic synthetic route, and the possibility of its self-assembly was verified by ultraviolet–visible and fluorescence spectroscopy using pyrene as the hydrophobic probe. Transmission electron microscopy and scanning electron microscopy indicated that aggregation morphologies of these self-assemblies were thin disks with radii from 250 to 500 nm. Section analysis of atomic force microscopy for a thin disk gave a thickness of approximately 16 nm. The existence of hydrogen bonds among the pendants was investigated by infrared spectra and Gaussian calculation. Cellular uptake assay observed by confocal laser scanning microscopy and cell cytotoxicity tests by MTT dye reduction method showed that the self-assemblies had an evident hepatoma-targeting function to hepG2 human hepatoma cells and could effectively realize cellular internalization of azacitidine.