a sterically stabilized immunolipoplex for systemic administration of a therapeutic gene a sterically stabilized immunolipoplex tsplp containing an antitransferrin receptor singlechain antibody fragment tfrscfvpeg molecule has been developed to specifically and efficiently deliver a therapeutic gene to tumor cells a postcoating preparation strategy was employed in which a dnalipid complex lipoplex was formed first and then sequentially conjugated with peg and tfrscfv the complex prepared by this method was shown to be superior in ability to deliver genes to tumor cells than when prepared by a common precoating strategy in which dna is mixed with tfrscfvpeg conjugated liposome using prostate cancer cell line du145 a comparison was made between the in vitro and in vivo gene delivery efficiencies of four complexes lipoplex lp peglipoplex plp tfrscfvpeglipoplex tsplp and our standard tfrscfvlipoplex tslp in vitro the order of transfection efficiency was tslplp approximately tsplpplp however in vivo the order of transfection efficiency after systemic administration via the tail vein was tsplptslplp or plp with tsplpmediated exogenous gene expression in tumor being twofold higher than when mediated by tslp this suggests that the in vitro transfection efficiency of tsplp was not indicative of its in vivo efficiency in addition it was found that the level of exogenous gene expression in the tumor mediated by tsplp was higher than that mediated by tslp and did not decrease over the time more importantly high exogenous gene expression in tumor but low expression in liver was observed after an iv delivery of tsplp carrying either the gfp reporter gene or the p53 gene indicating that tumor preferential targeting was maintained by this complex in the presence of peg these findings show that incorporation of peg into our targeted lipoplex results in a more efficient delivery of the complex to the tumor cells possibly by inhibiting the first pass clearance observed with nonpeg containing liposomes therefore these data demonstrate that tsplp is a improvement over our previously established tumor targeted gene delivery complex for systemic gene therapy of cancer