fig , confocal fluorescence images of bt cells stained with effexor feel hot mitotracker red after exposure for lohrs to dna green complexed with cdqasomes left column circular mlspdna conjugate, right column linearized mlspdna conjugate top row a and b red channel, middle row effexor feel hot c and d green channel, bottom row e and f effexor feel hot corresponding overlaid images figure shows confocal fluorescence micrographs of cells incubated with mlspdna conjugates, which were vectorized with vesicles made from effexor feel hot the cyclohexyl derivative of dequalinium cdqasomes for the cell exposures imaged in the left column panels �, � and e effexor feel hot the nonrestricted, ie circular form of pdna was used, while for the experiments pictured in the right column panels b, d effexor feel hot and f, the plasmid dna was linearized before dqaplex formation effexor feel hot the characteristic red mitochondrial staining pattern panels a and b shows the functional viability of the imaged cells and the intracellular effexor feel hot green fluorescence panels � and d demonstrates efficient cell internalization of the fluorescein labeled dna the green and red fluorescence channels effexor feel hot were then overlaid to produce the composite image seen in panels e and f, where the regions of true colocalization effexor feel hot of red and green fluorescence were pseudocolored in white for better effexor feel hot visualization strikingly, in the overlaid images, there is hardly any green fluorescence detectable nearly all areas of green fluorescence in panels � and d appeared as white areas in panels e and f, strongly suggesting that almost the entire dna has effexor feel hot 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 effexor feel hot both mitochondrial membranes, and therefore would potentially be accessible to effexor feel hot the mitochondrial transcription machinery, remains yet to be determined dqasomes effexor feel hot as carriers of proapoptotic drugs dysregulation of the apoptotic machinery is effexor feel hot generally accepted as an almost universal component of the transformation process of normal cells into cancer cells and a large effexor feel hot body of experimental data demonstrates that mitochondria play a key role effexor feel hot in the complex apoptotic mechanism consequently, any therapeutic strategy aimed effexor feel hot at specifically triggering apoptosis in cancer cells is believed to effexor feel hot have potential therapeutic effect, several clinically approved drugs such as vp effexor feel hot etoposide, arsenite and vinorelbine, as well as an increasing number effexor feel hot of experimental anticancer drugs reviewed by constantini et al, such as betulinic acid, lonidamine, ceramide and cd have been found to effexor feel hot act directly on mitochondria, resulting in triggering apoptosis in order to maximize the therapeutic potential of such anticancer drugs, which 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 effexor feel hot to act directly on mitochondria may trigger apoptosis in circumstances effexor feel hot in which conventional drugs fail to act, because endogenous, upstream of effexor feel hot 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 released at the particular intracellular site of action, ie mitochondria effexor feel hot 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, effexor feel hot 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 published most recently in this study, paclitaxel was chosen as effexor feel hot a model compound paclitaxel is known as a potent antitubulin agent effexor feel hot used in the treatment of malignancies its therapeutic potential, however, effexor feel hot is limited due to a very narrow span between the effexor feel hot maximal tolerated dose and intolerable toxic levels in addition, its poor aqueous solubility requires the formulation of emulsions containing cremophor el�, an oil of considerable toxicity by itself recently, it has effexor feel hot been demonstrated that clinically relevant concentrations of paclitaxel target mitochondria directly and trigger apoptosis by inducing cytochrome � release in a effexor feel hot permeability transition pore ptpdependent manner this mechanism of action is effexor feel hot known from the other proapoptotic, directly on mitochondria acting agents a effexor feel hot 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 effexor feel hot considered a prime candidate to benefit from a mitochondriaspecific drug delivery system such as dqasomes it was demonstrated that paclitaxel can be incorporated into dqasomes at a stoichiometric molar ratio of effexor feel hot paclitaxel 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 effexor feel hot sample show a remarkable conformity worm or rodlike structures approximately nm in length, the size of which could also be confirmed effexor feel hot 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 lexapro makes me drowsy panel size effexor feel hot distribution analysis of identical preparation shown in left panel the formation effexor feel hot of wormlike micelles as described for selfassembling amphiphilic block copolymers effexor feel hot appears possible � s � i in a preliminary study, effexor feel hot paclitaxelloaded dqasomes were tested for their ability to inhibit the growth effexor feel hot of human colon cancer cells in nude mice for controls effexor feel hot with free paclitaxel, the drug was suspended in dmso at effexor feel hot mm, stored at �c and immediately diluted in warm medium before use in all controls, the respective dose of free paclitaxel and empty dqasomes was adjusted according to the dose of effexor feel hot paclitaxel and dequalinium given in the paclitaxelloaded dqasome sample due to effexor feel hot the lack of any inhibitory effect on tumor growth, the dose was tripled after weeks figure shows that at concentrations effexor feel hot where free paclitaxel and r hepes buffer v free paclitaxel empty dqasomes ?