fig , confocal fluorescence images of bt cells stained with 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 c and d green channel, bottom row e and f phoslo medicare part d pap 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 phoslo medicare part d pap imaged in the left column panels �, � and e the nonrestricted, ie circular form of pdna was used, while for phoslo medicare part d pap the experiments pictured in the right column panels b, d and f, the plasmid dna was linearized before dqaplex formation phoslo medicare part d pap 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 panels e and f, where the regions of true colocalization of red and green fluorescence were pseudocolored in white for better phoslo medicare part d pap visualization strikingly, in the overlaid images, there is hardly any phoslo medicare part d pap green fluorescence detectable nearly all areas of green fluorescence in phoslo medicare part d pap panels � and d appeared as white areas in panels e and f, strongly suggesting that almost the entire dna has phoslo medicare part d pap 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 as carriers of proapoptotic drugs dysregulation of the apoptotic machinery is generally accepted as an almost universal component of the transformation phoslo medicare part d pap process of normal cells into cancer cells and a large phoslo medicare part d pap body of experimental data demonstrates that mitochondria play a key role in the complex apoptotic mechanism consequently, any therapeutic strategy aimed phoslo medicare part d pap at specifically triggering apoptosis in cancer cells is believed to phoslo medicare part d pap have potential therapeutic effect, several clinically approved drugs such as vp etoposide, arsenite and vinorelbine, as well as an increasing number phoslo medicare part d pap 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 phoslo medicare part d pap 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 phoslo medicare part d pap as the subcellular level firstly, the delivery of drugs known phoslo medicare part d pap to act directly on mitochondria may trigger apoptosis in circumstances phoslo medicare part d pap in which conventional drugs fail to act, because endogenous, upstream of phoslo medicare part d pap 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 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, phoslo medicare part d pap they could provide the basis for a doubletargeting effect of dqasomes, ie on the cellular level normal cells vs carcinoma phoslo medicare part d pap 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 a model compound paclitaxel is known as a potent antitubulin agent used in the treatment of malignancies its therapeutic potential, however, phoslo medicare part d pap 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 been demonstrated that clinically relevant concentrations of paclitaxel target mitochondria directly phoslo medicare part d pap and trigger apoptosis by inducing cytochrome � release in a phoslo medicare part d pap permeability transition pore ptpdependent manner this mechanism of action is phoslo medicare part d pap known from the other proapoptotic, directly on mitochondria acting agents a phoslo medicare part d pap hour delay between the treatment with paclitaxel or with other phoslo medicare part d pap ptp inducers, and the release of cytochrome � in cellfree phoslo medicare part d pap systems, compared with intact cells, has been explained by the existence phoslo medicare part d pap of several drug targets inside the cell, making only a phoslo medicare part d pap 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 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 phoslo medicare part d pap 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 phoslo medicare part d pap in length, the size of which could also be confirmed by the size distribution analysis shown in fig , right panel phoslo medicare part d pap 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 phoslo medicare part d pap of wormlike micelles as described for selfassembling amphiphilic block copolymers phoslo medicare part d pap appears possible � s � i in a preliminary study, paclitaxelloaded dqasomes were tested for their ability to inhibit the growth of human colon cancer cells in nude mice for controls with free paclitaxel, the drug was suspended in dmso at phoslo medicare part d pap mm, stored at �c and immediately diluted in warm medium before use in all controls, the respective dose of free paclitaxel phoslo medicare part d pap 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 dose was tripled albuterol caused uri after weeks figure shows that at concentrations where free paclitaxel and r hepes buffer v free paclitaxel empty dqasomes ?