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