fig , confocal fluorescence images of can caffeine make you fat bt cells stained with mitotracker red after exposure for lohrs to dna green complexed with cdqasomes left column circular mlspdna conjugate, right column linearized synthroid dentist 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 synthroid dentist incubated with mlspdna conjugates, which were vectorized with vesicles made from the cyclohexyl derivative of dequalinium cdqasomes for the cell exposures synthroid dentist 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 synthroid dentist 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 synthroid dentist 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 synthroid dentist visualization strikingly, in the overlaid images, there is hardly any synthroid dentist green fluorescence detectable nearly all areas of green fluorescence in synthroid dentist panels � and d appeared as white areas in panels e synthroid dentist and f, strongly suggesting that almost the entire dna has been delivered not only towards mitochondria, but also into the synthroid dentist organelle however, whether all or at least a portion of the synthroid dentist 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 synthroid dentist generally accepted as an almost universal component of the transformation process of normal cells into cancer cells and a large body of experimental data demonstrates that mitochondria play a key role synthroid dentist in the complex apoptotic mechanism consequently, any therapeutic strategy aimed synthroid dentist at specifically triggering apoptosis in cancer cells is believed to synthroid dentist have potential therapeutic effect, several clinically approved drugs such as vp etoposide, arsenite and vinorelbine, as well as an increasing number synthroid dentist of experimental anticancer drugs reviewed by constantini et al, such as betulinic acid, lonidamine, ceramide and cd have been found to synthroid dentist act directly on mitochondria, resulting in triggering apoptosis in order to maximize the therapeutic potential of such anticancer drugs, which synthroid dentist 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 synthroid dentist as the subcellular level firstly, the delivery of drugs known synthroid dentist to act directly on mitochondria may trigger apoptosis in circumstances synthroid dentist in which conventional drugs fail to act, because endogenous, upstream of mitochondria apoptosis induction pathways are disrupted secondly, transporting the cytotoxic drug to its intracellular target could overcome multidrug resistance by synthroid dentist hiding the drug inside the delivery system until it becomes selectively synthroid dentist 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 synthroid dentist dqasomes, ie on the cellular level normal cells vs carcinoma cells, and on the subcellular level mitochondria versus nucleus first data synthroid dentist involving the encapsulation of anticancer drugs into dqasomes have been synthroid dentist published most recently in this study, paclitaxel was chosen as synthroid dentist a model compound paclitaxel is known as a potent antitubulin agent synthroid dentist 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 synthroid dentist aqueous solubility requires the formulation of emulsions containing cremophor el�, an oil of considerable toxicity by itself recently, it has synthroid dentist been demonstrated that clinically relevant concentrations of paclitaxel target mitochondria directly and trigger apoptosis by inducing cytochrome � release in a synthroid dentist permeability transition pore ptpdependent manner this mechanism of action is synthroid dentist known from the other proapoptotic, directly on mitochondria acting agents a synthroid ambien with coumadin dentist hour delay between the treatment with paclitaxel or with other synthroid dentist ptp inducers, and the release of cytochrome � in cellfree synthroid dentist 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 considered a prime candidate to benefit from a mitochondriaspecific drug delivery synthroid dentist 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, synthroid dentist 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 synthroid dentist 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 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 of wormlike micelles as described for selfassembling amphiphilic block copolymers synthroid dentist 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 synthroid dentist with free paclitaxel, the drug was suspended in dmso at synthroid dentist mm, stored at �c and immediately diluted in warm medium before use in all controls, the respective dose of free paclitaxel synthroid dentist and empty dqasomes was adjusted according to the dose of synthroid dentist paclitaxel and dequalinium given in the paclitaxelloaded dqasome sample due to synthroid dentist the lack of any inhibitory effect on tumor growth, the dose was tripled after weeks figure shows that at concentrations synthroid dentist where free paclitaxel and r hepes buffer v free paclitaxel empty dqasomes ?