The reduction-triggered degradable poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine)/polyethyleneimine (P(MAA-co-BAC)/PEI) microcapsules were prepared by distillation-precipitation polymerization for delivery of anti-cancer drug and gene. N,N-bis(acryloyl)cystamine (BAC) as a crosslinker containing a disulfide bond can be triggered by reductive agents, such as glutathione (GSH) and dithiothreitol (DTT), to endow the functional microcapsules with reduction-triggered drug release. The P(MAA-co-BAC)/PEI microcapsules were characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectra (FT-IR), laser particle size analyzer and elemental analysis. The degradable behavior of microcapsules was investigated by analysis of UV-vis spectroscopy. The controlled drug release behavior for P(MAA-co-BAC)/PEI microcapsules was strongly dependent on the absence/presence of GSH and the pH values with doxorubicin hydrochloride (DOX) as a model drug molecule. The in vitro gene transfection ability was evaluated by Hela cells with the transfection of plasmid DNA (pDNA) encoded with green fluorescent protein (GFP) and the transfection efficiency was determined by confocal fluorescence microscopy. Furthermore, the cytotoxicities of (P(MAA-co-BAC)/PEI) microcapsules before and after loading of DOX were assessed via WST-1 assay. The P(MAA-co-BAC)/PEI microcapsules provide the potential novel vectors for delivery of drugs and genes, promising for future applications in anticancer drug and gene combined therapy. (C) 2013 Elsevier Ltd. All rights reserved.