Mitochondria are regarded as the powerhouse of the cell because they generate a majority of the cell’s energy in the form of ATP. They also play important roles in regulating apoptotic cell death, the formation of free radicals, regulating the cell cycle, and calcium metabolism. Mitochondrial dysfunction has been linked to a variety of disease states including cancer, cardiovascular disease, and neurodegenerative diseases. Because of this, mitochondria have become an encouraging intracellular target for drug delivery in recent years. [1, 2] There are several anticancer agents that act directly on mitochondria. Paclitaxel, etoposide, vinorelbine, vinblastine, ceramide, and lonidamine are a few examples of anticancer agents that directly target …show more content…
The MITO-Porter liposomes are conjugated with octarginine residues that facilitate the nanocarrier’s entry into cells via macropinocytosis. The carrier then escapes the endosome into the cytosol using membrane fusion. The carrier can then bind to mitochondrial membranes through electrostatic interactions with octaarginine. Once fused with the mitochondrial membrane, encapsulated compounds are delivered inside the mitochondria. [3, 8] Yamada et al. demonstrated MITO-Porter’s ability to deliver macromolecules into mitochondria. Green fluorescent protein (GFP) was encapsulated within MITO-Porter and was tested HeLa cells. MITO-Porter was able to successfully deliver GFP inside mitochondria. Similar results were seen when colloidal gold particles were used in place of GFP. [8] Another study by Yamada et al. demonstrated MITO-Porters ability to deliver bongkrekic acid, an antiapoptotic toxin, to mitochondria. The BKA-MITO-Porter was able to target mitochondria and reduce apoptosis in HeLa cells whereas naked BKA did …show more content…
The hydrophobic core of a micelle serves as a suitable carrier for water insoluble drugs while the outer hydrophilic layer helps it disperse into aqueous media. [13] A study by Sharma et al. suggested that micelles could be used for drug delivery to mitochondria. Researchers synthesized micelle nanocarriers based on ABC miktoarm polymers (A=polyethylene glycol (PEG), B=polycaprolactone (PCL), C=triphenylphosphonium bromide (TPPBr)) then loaded them with CoQ10, an antioxidant capable of reducing mitochondrial ROS. The mitochondrial-targeted mitkoarm carrier was successful in localizing within mitochondria as evidenced by confocal microscopy. An MTT assay was used to investigate the nanocarrier’s effects on mitochondrial metabolic activity. Targeted micelles containing CoQ10 and CoQ10 alone were shown to improve mitochondrial metabolic activity at low concentrations (<5 µM), whereas higher concentrations were shown to be deleterious to mitochondrial activity. Using confocal microscopy, it was shown that CoQ10 targeted micelles reduced superoxide anion generated by H2O2 in primary hippocampal cells.[14] In a recent study, researchers prepared doxorubicin-loaded pH-responsive micelles to study their effects on overcoming drug resistance in breast cancer cells in vitro and in vivo. The micelles were prepared from a pH-responsive diblock copolymer (PEG-b-PDPA) and a mitochondrial targeting vitamin E derivative (TPGS). Doxorubicin
Pinto Reis C., Neufeld RJ., Ribeiro AJ., & Veiga F., 2006. Nanoencapsulation I. Method for preparation of drug-loaded polymeric nanoparticles. Nanomedicine: Nanotechnology, Biology and Medicine, 2, 9-21
It’s proposed by many experiments that mitochondrial dysfunction contributes to neuropathic symptoms which are produced by various chemotherapeutic agents. It is suggested that neural apoptosis maybe through the intrinsic pathway or extrinsic.
The main idea of this study is to underscore: "the need to validate potential cellular targets for adjuvant and systemic therapies on disseminated cancer cells directly"( Cancer Cell: July 2003).
...om aggregation and floating behavior of drug particles during dissolution. All proliposomal powders showed 67.5 to 91.2% drug release with following order KPL3>KPL5>KPL0>KPL4>Pure drug within 5 min which indicated improved dissolution of drug in the form of proliposomes. The improved dissolution of ketoprofen in proliposomal formulation may be due to the hydrophilic nature of pearlitol which facilitate the quick hydration of proliposomes to transform into liposomes, enhanced solubility of poorly water soluble drug by amphiphilic HSPC or altered physical state of drug entrapped in the bilayers from crystalline to amorphous state and it may be also due to increased effective surface area and wetting characteristic of unentrapped drug upon contact with dissolution medium as fine dispersion which was adsorbed over the porous water soluble carrier i.e. pearlitol SD 200.
The structures of liposomes are spherical and are usually between 15nm and 1000 nm in diameter. They are able to target the ligands that are attached to their surface to direct them to the appropriate sites wi...
...des dissolving of 100mg of PC into 15 ml ethanol and then this solution mixture is added drop-wise into a Vitamin C solution. Continuous stirring is required. The conditions like low temperature and moisture content can be achieved. The organic solvent is then evaporated and by maintaining pH at 7.4 of the phosphate buffer solution (PBS), the solvent traces are removed. The Liposome dispersion is then stored under vacuum overnight. The liposome size can be downsized by sonication. Liposome characterisation i.e. size and surface structure can be observed using cryo-transmission electron microscopy (cryo-TEM) (27).
Christian M. Kurbacher helps supprort this claim with MCF-7 breast cells. When vitamin C was added to cytostatic drugs cisplatin, doxorubicin and paclititaxel, results indicated that chemotherapeutic drugs are more effective (41). Additionally, as high doses of vitamin are not toxic, this allows for a large range of potential chemotherapeutic drugs. While, sensitivity and cytostatic drugs are yet to be tested on melanoma cell lines, the future looks bright for prospective cytostatic+ vitamin C combinations.
Because the body, namely the “brain, heart, liver, kidneys, pancreas, and skeletal muscle, demand a finely tuned capacity for energy and lots of it, these tissues possess more mitochondria” (parkridge). When the mitochondria are not properly functioning for these organs, cell damage can occur.
...dependent on the conversion of yellow tetrazolium bromide to its purple formazan derivative by mitochondrial succinate dehydrogenase in viable cells [34].
Oxidative stress is critical as it is extensively related to human diseases, such as rheumatoid arthritis, Alzheimer’s, Parkinson’s, diabetes, cataract, aging and cancer (Zhao and Zha...
showed that phosphorlyation is not neccessary for Smo translocation but rather inhibition of Smo endocytosis was sufficient to drive Smo to the plasma membrane. This was observed by fluorescently labelling Smo with GFP and tracking its location following either treatment with Hh or Dynasore, a pharmacological inhibitor of dynamin-mediated endocytosis (Macia et al., 2006). In both cases Smo translocated to the plasma membrane. The same was done for a nonphosphorylatable SmoSA-GFP fusion in which the inhibition of endocytosis by treatment with Dynasore caused SmoSA to translocation to the plasma membrane. The observation that SmoSA can also be present at the membrane demonstrates that some exchange between the intracellular and plasma membrane bound pools must also occur for nonphosphorylated
The mitochondria is an organelle which is generally an oval shape and is found inside the cytoplasm and is again apart of the eukaryotic cells. The main function of the mitochondria is to complete cellular respiration; in simple terms it acts like a digestive system to break down essential nutrients and to convert it into energy. This energy is usually found to in ATP which is a rich molecule taken from the energy stored in food. Furthermore, mitochondria stores calcium for signalling activities; such as heat, growth and death. They have two unique membranes and mitochondria isn’t found in human cells like the red blood cells yet liver and muscle cells are filled entirely with mitochondria.
can be used directly by the cell as an energy source. Mitochondria tend to be
The neurodegenerative diseases include a wide range of acute and chronic conditions in which there is a loss of neurons or and glial cells in the brain and spinal cord. For example, there is a loss of dopamine neurons in Parkinson’s disease, and motor neurons in Amyotrophic Lateral Sclerosis.1 The study we will be conducted is intended to research on how gender affect transfer of mitochondrial, and or exosomes as a stem cell repair mechanism in neurodegenerative diseases.
Cells are the basic building blocks of all living things. The human body is composed of trillions of cells. They provide structure for the body, take in nutrients from food, convert those nutrients into energy, and carry out specialized functions. But it also contains highly organized physical structures which are called intracellular organelles. These organelles are important for cellular function. For instance Mitochondria is the one of most important organelle of the cell. Without Mitochondria more than 95% of the cell’s energy, which release from nutrients would cease immediately [Guyton et al. 2007].