Nanosized carriers based on amphiphilic poly-N-vinyl-2-pyrrolidone for intranuclear drug delivery

AIM: Ability to deliver drugs into the cell nuclei can significantly increase the efficacy of cancer therapies, in particular in the case of multidrug-resistant cancer Results: Polymer nanocarriers based on amphiphilic thiooctadecyl-terminated poly-N-vinyl-2-pyrrolidone were produced and loaded with a model hydrophobic drug, curcumin. Two commonly used loading approaches - emulsification and ultrasonic dispersion - were found to lead to two different size distributions with distinctively different biological effect. While nanocarriers produced via the emulsion method penetrated cells by dynamin-dependent endocytic mechanisms, sub-100 nm dispersion-produced nanocarriers were capable of crossing the membranes via biologically independent mechanisms.CONCLUSION: This finding opens an intriguing possibility of intranuclear delivery by merely tailoring the size of polymeric carriers, thus promising a new approach for cancer therapies.</p

Domestication and growth hormone transgenesis cause similar changes in gene expression in coho salmon (Oncorhynchus kisutch)

Domestication has been extensively used in agricultural animals to modify phenotypes such as growth rate. More recently, transgenesis of growth factor genes [primarily growth hormone (GH)] has also been explored as a rapid approach to accelerating performance of agricultural species. Growth rates of many fishes respond dramatically to GH gene transgenesis, whereas genetic engineering of domestic mammalian livestock has resulted in relatively modest gains. The most dramatic effects of GH transgenesis in fish have been seen in relatively wild strains that have undergone little or no selection for enhanced growth, whereas genetic modification of livestock necessarily has been performed in highly domesticated strains that already possess very rapid growth. Such fast-growing domesticates may be refractory to further stimulation if the same regulatory pathways are being exploited by both genetic approaches. By directly comparing gene expression in wild-type, domestic, and GH transgenic strains of coho salmon, we have found that domestication and GH transgenesis are modifying similar genetic pathways. Genes in many different physiological pathways show modified expression in domestic and GH transgenic strains relative to wild-type, but effects are strongly correlated. Genes specifically involved in growth regulation (IGF1, GHR, IGF-II, THR) are also concordantly regulated in domestic and transgenic fish, and both strains show elevated levels of circulating IGF1. Muscle expression of GH in nontransgenic strains was found to be elevated in domesticated fish relative to wild type, providing a possible mechanism for growth enhancement. These data have implications for genetic improvement of existing domesticated species and risk assessment and regulation of emerging transgenic strains