fig , confocal fluorescence images of bt cells stained with mitotracker red after exposure for lohrs to dna green complexed wellbutrin breastfeeding with cdqasomes left column circular mlspdna conjugate, right column linearized wellbutrin breastfeeding mlspdna conjugate top row a and b red channel, middle row wellbutrin breastfeeding c and d green channel, bottom row e and f corresponding overlaid images figure shows confocal fluorescence micrographs of cells incubated with mlspdna conjugates, which were vectorized with vesicles made from wellbutrin breastfeeding 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 the characteristic red mitochondrial staining pattern panels a and b shows 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 were then overlaid to produce the composite image seen in wellbutrin breastfeeding 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 panels � and d appeared as white areas in panels e and f, strongly suggesting that almost the entire dna has been delivered not only towards mitochondria, but also into the wellbutrin breastfeeding organelle however, whether all or at least a portion of the wellbutrin breastfeeding pdna has actually entered the mitochondrial matrix, ie has crossed wellbutrin breastfeeding 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 wellbutrin breastfeeding generally accepted as an almost universal component of the transformation wellbutrin breastfeeding 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 topamax central coast weight loss in cancer cells is believed to wellbutrin breastfeeding have potential therapeutic effect, several clinically approved drugs such as vp etoposide, arsenite and vinorelbine, as well as an increasing number wellbutrin breastfeeding of experimental anticancer drugs reviewed by constantini et al, such as betulinic acid, lonidamine, ceramide and cd have been found to 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 wellbutrin breastfeeding as the subcellular level firstly, the delivery of drugs known wellbutrin breastfeeding 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 wellbutrin breastfeeding drug to its intracellular target could overcome multidrug resistance by wellbutrin breastfeeding hiding the drug inside the delivery system until it becomes selectively released at the particular intracellular site of action, ie mitochondria wellbutrin breastfeeding 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, wellbutrin breastfeeding 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 wellbutrin breastfeeding involving the encapsulation of anticancer drugs into dqasomes have been wellbutrin breastfeeding 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 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 wellbutrin breastfeeding been demonstrated that clinically relevant concentrations of paclitaxel target mitochondria directly wellbutrin breastfeeding and trigger apoptosis by inducing cytochrome � release in a permeability transition pore ptpdependent manner this mechanism of action is wellbutrin breastfeeding known from the other proapoptotic, directly on mitochondria acting agents a hour delay between the treatment with paclitaxel or with other wellbutrin breastfeeding 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 wellbutrin breastfeeding subset of the drug available for mitochondria consequently, paclitaxel was considered a prime candidate to benefit from a mitochondriaspecific drug delivery wellbutrin breastfeeding system such as dqasomes it was demonstrated that paclitaxel can wellbutrin breastfeeding be incorporated into dqasomes at a stoichiometric molar ratio of paclitaxel to dequalinium considering the known spherical character of dqasomes, wellbutrin breastfeeding the results of an electron microscopic em analysis of dequasomal incorporated wellbutrin breastfeeding paclitaxel, however, seem rather surprising the transmission em image fig , wellbutrin breastfeeding left panel and the cryoem image fig of an identical wellbutrin breastfeeding sample show a remarkable conformity worm or rodlike structures approximately nm in length, the size of which could also be confirmed by the size distribution analysis shown in fig , right panel the molecular structureof this wormlike complex remains to be determined nevertheless wellbutrin breastfeeding fig left panel transmission electron microscopic image uranyl acetate staining of dqasomal incorporated paclitaxel mol taxolmol dequalinium right panel size wellbutrin breastfeeding distribution analysis of identical preparation shown in left panel the formation wellbutrin breastfeeding of wormlike micelles as described for selfassembling amphiphilic block copolymers wellbutrin breastfeeding appears possible � s � i in a preliminary study, paclitaxelloaded dqasomes were tested for their ability to inhibit the growth wellbutrin breastfeeding of human colon cancer cells in nude mice for controls wellbutrin breastfeeding with free paclitaxel, the drug was suspended in dmso at wellbutrin breastfeeding 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 paclitaxel and dequalinium given in the paclitaxelloaded dqasome sample due to the lack of any inhibitory effect on tumor theophylline created drug resistance growth, the dose was tripled after weeks figure shows that at concentrations where free paclitaxel and r hepes buffer v free paclitaxel empty dqasomes ?