fig , confocal fluorescence images of bt cells stained with prednisone and half life mitotracker red after exposure for lohrs to dna green complexed prednisone and half life with cdqasomes left column circular mlspdna conjugate, right column linearized mlspdna conjugate top row a and b red channel, middle row prednisone and half life c and d green channel, bottom row e and f prednisone and half life corresponding overlaid images figure shows confocal fluorescence micrographs of cells incubated with mlspdna conjugates, which were vectorized with vesicles made from the cyclohexyl derivative of dequalinium cdqasomes for the cell exposures prednisone and half life imaged in the left column panels �, � and e prednisone and half life the nonrestricted, ie circular form of pdna was used, while for the experiments pictured in the right column panels b, d and f, the plasmid dna was linearized before dqaplex formation the characteristic red mitochondrial staining pattern panels a and b shows prednisone and half life the functional viability of the imaged cells and the intracellular green fluorescence panels � and d demonstrates efficient cell internalization of the fluorescein labeled dna the green and red fluorescence channels prednisone and half life were then overlaid to produce the composite image seen in panels e and f, where the regions of true colocalization of red and green fluorescence were pseudocolored in white for better prednisone and half life visualization strikingly, in the overlaid images, there is hardly any prednisone and half life green fluorescence detectable nearly all areas of green fluorescence in panels � and d appeared as white areas in panels e prednisone and half life and f, strongly suggesting that almost the entire dna has been delivered not only towards mitochondria, but also into the organelle however, whether all or at least a portion of the pdna has actually entered the mitochondrial matrix, ie has crossed both mitochondrial membranes, and therefore would potentially be accessible to the mitochondrial transcription machinery, remains yet to be determined dqasomes prednisone and half life as carriers of proapoptotic drugs dysregulation of the apoptotic machinery is generally accepted as an almost universal component of the transformation prednisone and half life process of normal cells into cancer cells and a large body of experimental data demonstrates that mitochondria play a key role prednisone and half life in the complex apoptotic mechanism consequently, any therapeutic strategy aimed prednisone and half life at specifically triggering apoptosis in cancer cells is believed to have potential therapeutic effect, several clinically approved drugs such as vp prednisone and half life etoposide, arsenite and vinorelbine, as well as an increasing number of experimental anticancer drugs reviewed by constantini et al, such prednisone and half life as betulinic acid, lonidamine, ceramide and cd have been found to prednisone and half life act directly on mitochondria, resulting in triggering apoptosis in order prednisone and half life to maximize the therapeutic potential of such anticancer drugs, which are known to act at or inside mitochondria, the use of prednisone and half life dqasomes as a mitochondriaspecific drug delivery system has been proposed hypothetically, dqasomebased anticancer chemotherapy entails features which would make it putatively superior to conventional chemotherapeutic approaches on the cellular, as well prednisone and half life as the subcellular level firstly, the delivery of drugs known to act directly on mitochondria may trigger apoptosis in circumstances prednisone and half life in which conventional drugs fail to act, because endogenous, upstream of mitochondria apoptosis induction pathways are disrupted secondly, transporting the cytotoxic drug to its intracellular target could overcome multidrug resistance by hiding the drug inside the delivery system until it becomes selectively prednisone and half life released at the particular intracellular site of action, ie mitochondria prednisone and half life thirdly, many carcinoma cells, including human breast adenocarcinoma derived cells, have an elevated plasma membrane potential relative to their normal prednisone and half life parent cell lines in addition to the higher mitochondrial membrane potential, they could provide the basis for a doubletargeting effect of dqasomes, ie on the cellular level normal cells vs carcinoma cells, and on the subcellular level mitochondria versus nucleus first data prednisone and half life involving the encapsulation of anticancer drugs into dqasomes have been published most recently in this study, paclitaxel was chosen as a model compound paclitaxel is known as a potent antitubulin agent used in the treatment of malignancies its therapeutic potential, however, is limited due to a very narrow span between the prednisone and half life maximal tolerated dose and intolerable toxic levels in addition, its poor aqueous solubility requires the formulation of emulsions containing cremophor el�, prednisone and half life an oil of considerable toxicity by itself recently, it has prednisone and half life been demonstrated that clinically relevant concentrations of paclitaxel target mitochondria directly prednisone and half life and trigger apoptosis by inducing cytochrome � release in a permeability transition pore ptpdependent manner this mechanism of action is known from the other proapoptotic, directly on mitochondria acting agents a hour delay between the treatment with paclitaxel or with other ptp inducers, and the release of cytochrome � in cellfree systems, compared with intact cells, has been explained by the existence of several drug targets inside the cell, making only a subset of the drug available for mitochondria consequently, paclitaxel was considered a prime candidate to benefit from a mitochondriaspecific drug delivery system such as dqasomes it was demonstrated that paclitaxel can prednisone and half life be incorporated into dqasomes at a stoichiometric molar ratio of paclitaxel online soma servers to dequalinium considering the known spherical character of dqasomes, the results of an electron microscopic em analysis of dequasomal incorporated paclitaxel, however, seem rather surprising the transmission em image fig , left panel and the cryoem image fig of an identical sample show a remarkable conformity worm or rodlike structures approximately nm prednisone and half life in length, the size of which could also be confirmed prednisone and half life by the size distribution analysis shown in fig , right panel prednisone and half life the molecular structureof this wormlike complex remains to be determined nevertheless prednisone and half life fig left panel transmission electron microscopic image uranyl acetate staining prednisone and half life of dqasomal incorporated paclitaxel mol taxolmol dequalinium right panel size distribution analysis of identical preparation shown in left panel the formation of wormlike micelles as described for selfassembling amphiphilic block copolymers appears possible � s � i in a preliminary study, prednisone and half life paclitaxelloaded dqasomes were tested for their ability to inhibit the growth of human colon cancer cells in nude mice for controls prednisone and half life with free paclitaxel, the drug was suspended in dmso at mm, stored at �c and immediately diluted in warm medium before prednisone and half life use in all controls, the respective dose of free paclitaxel prednisone and half life and empty dqasomes was adjusted according to the dose of paclitaxel and dequalinium given in the paclitaxelloaded dqasome sample due to the lack of any inhibitory effect on tumor growth, the prednisone and half life dose was tripled after weeks figure shows that at concentrations where free paclitaxel and r hepes buffer v free paclitaxel empty dqasomes ?