fig , confocal fluorescence images of bt cells stained with pravachol green tablets mitotracker red after exposure for lohrs to dna green complexed pravachol green tablets with cdqasomes left column circular mlspdna conjugate, right column linearized pravachol green tablets mlspdna conjugate top row a and b red channel, middle row pravachol green tablets c and d green channel, bottom row e and f pravachol green tablets 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 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 and f, the plasmid dna was linearized before dqaplex formation pravachol green tablets the characteristic red mitochondrial staining pattern panels a and b shows pravachol green tablets the functional viability of the imaged cells and the intracellular pravachol green tablets green fluorescence panels � and d demonstrates efficient cell internalization of the fluorescein labeled dna the green and red fluorescence channels pravachol green tablets were then overlaid to produce the composite image seen in pravachol green tablets 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 pravachol green tablets green fluorescence detectable nearly all areas of green fluorescence in pravachol green tablets panels � and d appeared as white areas in panels e pravachol green tablets 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 pravachol green tablets both mitochondrial membranes, and therefore would potentially be accessible to pravachol green tablets the mitochondrial transcription machinery, remains yet to be determined dqasomes pravachol green tablets as carriers of proapoptotic drugs dysregulation of the apoptotic machinery is generally accepted as an almost universal component of the transformation pravachol green tablets process of normal cells into cancer cells and a large body of experimental data demonstrates that mitochondria play a key role in the complex apoptotic mechanism consequently, any therapeutic strategy aimed at specifically triggering apoptosis in cancer cells is believed to have potential therapeutic effect, several clinically approved drugs such as vp pravachol green tablets etoposide, arsenite and vinorelbine, as well as an increasing number pravachol green tablets of experimental anticancer drugs reviewed by constantini et al, such as betulinic acid, lonidamine, ceramide and cd have been found to pravachol green tablets act directly on mitochondria, resulting in triggering apoptosis in order pravachol green tablets to maximize the therapeutic potential of such anticancer drugs, which pravachol green tablets are known to act at or inside mitochondria, the use of 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 as the subcellular level firstly, the delivery of drugs known pravachol green tablets to act directly on mitochondria may trigger apoptosis in circumstances in which conventional drugs fail to act, because endogenous, upstream of mitochondria apoptosis induction pathways are disrupted secondly, transporting the cytotoxic pravachol green tablets drug to its intracellular target could overcome multidrug resistance by pravachol green tablets hiding the drug inside the delivery system until it becomes selectively pravachol green tablets released at the particular intracellular site of action, ie mitochondria 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 cells, and on the subcellular level mitochondria versus nucleus first data involving the encapsulation of anticancer drugs into dqasomes have been pravachol green tablets published most recently in this study, paclitaxel was chosen as a model compound paclitaxel is known as a potent antitubulin agent pravachol green tablets used in the treatment of malignancies its therapeutic potential, however, pravachol green tablets is limited due to a very narrow span between the maximal tolerated dose and intolerable toxic levels in addition, its poor pravachol green tablets aqueous solubility requires the formulation of emulsions containing cremophor el�, pravachol green tablets an oil of considerable toxicity by itself recently, it has been demonstrated that clinically relevant concentrations of paclitaxel target mitochondria directly pravachol green tablets and trigger apoptosis by inducing cytochrome � release in a pravachol green tablets permeability transition pore ptpdependent giardiasis amoxicillin manner this mechanism of action is known from the other proapoptotic, directly on mitochondria acting agents a pravachol green tablets hour delay between the treatment with paclitaxel or with other pravachol green tablets 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 pravachol green tablets subset of the drug available for mitochondria consequently, paclitaxel was pravachol green tablets considered a prime candidate to benefit from a mitochondriaspecific drug delivery pravachol green tablets system such as dqasomes it was demonstrated that paclitaxel can pravachol green tablets be incorporated into dqasomes at a stoichiometric molar ratio of paclitaxel to dequalinium considering the known spherical character of dqasomes, the results of an electron microscopic em analysis of dequasomal incorporated pravachol green tablets 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 in length, the size of which could also be confirmed pravachol green tablets by the size distribution analysis shown in fig , right panel pravachol green tablets the molecular structureof this wormlike complex remains to be determined nevertheless pravachol green tablets fig left panel transmission electron microscopic image uranyl acetate staining of dqasomal incorporated paclitaxel mol taxolmol dequalinium right panel size pravachol green tablets distribution analysis of identical preparation shown in left panel the formation pravachol green tablets of wormlike micelles as described for selfassembling amphiphilic block copolymers pravachol green tablets appears possible � s � i in a preliminary study, paclitaxelloaded dqasomes were tested for their ability to inhibit the growth pravachol green tablets of human colon cancer cells in nude mice for controls with free paclitaxel, the drug was suspended in dmso at pravachol green tablets mm, stored at �c and immediately diluted in warm medium before pravachol green tablets use in all controls, the respective dose of free paclitaxel pravachol green tablets and empty dqasomes was adjusted according to the dose of pravachol green tablets paclitaxel and dequalinium given in the paclitaxelloaded dqasome sample due to pravachol green tablets the lack of any inhibitory effect on tumor growth, the pravachol green tablets dose was tripled after weeks figure shows that at concentrations where free paclitaxel and r hepes buffer v free paclitaxel empty dqasomes ?