Tumor Tissue And Healthy Tissue

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Nowadays, a lot of research teams are trying to develop new ways to treat cancer or to improve the efficacy of already existing treatment strategies. To do this, it is important to understand the differences between tumor tissue and healthy tissue. One of these differences concerns the pH in cancerous environment. In normal cells, intracellular pH is generally around 7,2 and thus lower than the extracellular pH of 7,4. Cancer tissue however shows a reversed pH gradient: the intracellular pH is increased (>7,4) and the extracellular pH is lower than usual (6,7-7,1). This gradient is maintained thanks to changes in the expression and activity of some particular plasma membrane ion pumps and transporters that facilitate the H+ efflux. Due to the increased intracellular pH, cell proliferation and the evasion of apoptosis is possible and the metabolic adaption is facilitated. Moreover, for efficient directed cell migration a higher intracellular pH is even obligatory. The decreased extracellular pH also offers some advantages for the development of the tumor : HCO3—-dependent buffering is limited, extracellular matrix remodeling is promoted and acid-activated proteases are stimulated which makes tumor cell invasion and dissemination easier (Webb e.a. 2011).

Another difference between tumor tissue and normal tissue is the glutathione concentration. Glutathione (GSH) is composed of three amino acids: cysteine, glycine and glutamate (see Figure 1.1). It is a very important antioxidant and is present in virtually every cell of the human body. The concentration of GSH is much higher intracellular (0,5-10 mM) than in the extracellular milieu (2-20 µM), and in tumor tissue GSH concentration is at least 4-fold higher than in normal tissue (F...

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...degree of intermolecular association. By adjusting the formulation or the chemical moieties of the drug delivery system, the moment and the location of the release of the drug may be controlled (You e.a. 2010).

The term nanocarriers includes a wide range of different nanosized drug delivery systems. The oldest and at the same time the most clinically established nanocarriers are liposomes, spheres composed of an aqueous core surrounded by one or more concentric lipid bilayers. They are suited for the encapsulation of both hydrophillic and hydrophobic drugs, respectively in the aqueous core and whitin the lipid membrane (Hafner e.a. 2014). Liposomes increase thus the solubility of hydrophobic compounds, they enable trapping of drug molecules with a high potency, they reduce systemic side effects and toxicity and they attenuate drug clearance (Riehemann e.a. 2009)

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