اندركنش يون فلزات سنگين، Zr(IV) و Hf(IV)، با داروي ضدسرطان پمتركسد تثبيت‌شده در سطح سامانه‌ي نانوساختار انتقال دارو، مطالعه شده با كمك روش‌هاي الكتروشيميايي و تجزيه سطح

Interaction of Heavy Metal Ions, Zr(IV) an‎d Hf(IV), with PMTXD Anti-Cancer Drug Immobilized on Nanostructured Drug-Delivery System Investigated by Electrochemical an‎d Surface Analysis Methods

شيمي تجزيه

The aim of this thesis is to investigate the interaction between a drug delivery system, consisting of pemetrexed immobilized on a gold electrode, an‎d heavy metal ions of Zr, Hf, Fe, Pb, As, an‎d Cd. Accordingly, in the first chapter, the behavior of heavy metal ions in relation to environmental an‎d pharmaceutical concerns, as well as their interaction with drug systems, is reviewed from the perspective of chemical literature. The importance of studying their interaction with the self-assembled monolayer system of pemetrexed is also discussed. In the second chapter, the practical method for modifying the electrode surface an‎d the fabrication of the monolayer system, gold-mercaptopropionic acid-pemetrexed (Au-MPA-PMTXD) is described. The procedure for collecting selec‎ted heavy metal ions on this drug system is then presented, along with the use of cyclic voltammetry (CV) an‎d differential pulse voltammetry (DPV) techniques an‎d the instruments employed. In the third chapter, the interaction of the prepared systems with the metal ions of Zr, Hf, Fe, As, Cd, an‎d Pb is individually examined. The data showed that these ions are adsorbed onto the Au-MPA-PMTXD system an‎d reduce the electrochemical activity of the drug (i.e., decrease the redox peak current an‎d move the peak potential to unfavorable direction). This behavior is attributed to the blocking of the drug active sites by the metal ions. The most significant surface blocking effect was observed with Zr an‎d Hf, followed by Cd, Pb, an‎d As, respectively. The Fe ion exhibited a different behavior: the oxidation peak potential of the system shifted from 0.208 V to a more favorable 0.021 V, most probably, due t different formation of Fe(II) an‎d Fe(III) with drug (similar to the behavior if well-know Fe-phenantheroline systems). Later in this chapter, the interaction of systems containing adsorbed Zr, Hf, an‎d Fe ions with MCF-7 cancer cells was investigated. According to these studies, Zr an‎d Fe ions-unlike Hf-enhanced the electrochemical activity of the drug in the presence of cancer cells. This suggests that in the presence of Zr an‎d Fe ions, the redox-active part of the drug remains uncomplexed an‎d electrochemically active. So, according to the obtained data, it can be concluded that the efficacy of pemetrexed in patients may be affected when exposed to environments contaminated with the mentioned heavy metals. Specifically, in the presence of Zr an‎d Hf ions, the drug appears to have little to no effect on cancer cells. Nevertheless, more comprehensive studies on this drug an‎d similar compounds in the presence of metal ions in living organisms an‎d cancer patients are required to further explore this issue. Finally, based on the conducted studies, the potential for sensor development using this system was eva‎luated. Since the magnitude of the drug redox signals is influenced by the adsorbed ions, it seems feasible to design, fabricate, an‎d study suitable sensors for some of these ions. However, this activity requires further investigation an‎d is beyond the defined scope of this thesis.

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