چكيده لاتين
Pemetrexed (PMTXD) is a multipurpose anticancer drug. The lack of selectivity in these drugs can lead to toxicity for healthy tissues, disrupt the treatment process, and cause irreversible complications during treatment. Therefore, the use of targeting agents has been considered as one of the effective methods in targeted drug delivery. In this regard, a targeted nanosystem consisting of the PMTXD and targeting agents; folic acid (FOA), glucosamine (GlcN), or glutamine (Gln), was designed through immobilization on a gold electrodesurface , and its interaction with MCF-7 cancer cells was studied in comparison with normal L929 cells.
In the first chapter, Accordingly, the literature was reviewed from this perspective. Our studies showed that gold is a biocompatible and inert surface and 3-mercaptopropionic acid (MPA) is a biocompatible and appropriate functional linker to immobilized PMTXD and the targeting agents on the surface, separately or adjacently (||) based on self-assembly technique, following up the interaction of the resulted nanosystems with cell lines.
In the second chapter, the chemicals, solution preparation, tools, devices and methods are mentioned and described. So, the gold electrode was prepared and cleaned using physical and electrochemical methods, then, the MPA self-assembled monolayers were used to attach the drug to the surface and form the Au-MPA-PMTXD||FOA, Au-MPA-PMTXD||GlcN, and Au-MPA-PMTXD||Gln nanosystems for the first time. The layer-by-layer formation of system was investigated using cyclic and differential pulse voltammetry (CV and DPV), electrochemical impedance spectroscopy (EIS), as well as attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Then, the interaction of the nanosystems with cancer and normal cell lines was followed via EIS technique in the presence of [Fe(CN)6]3/4 as a probe by following variations of the charge transfer resistance (Rct).
In the third chapter, the obtained data from electrochemical and surface analysis experiments are presented, analyzed, discussed. The results showed that the PMTXD, immobilized individually or in the vicinity of the targeting agents on the surface interacts with cancer cells expectedly. The EIS data showed that interaction of the PMTXD with cancer cells in the absence of the targeting agent (Au-MPA-PMTXD, Rct 1650.cm2) was significantly greater than its interaction with normal cells (Au-MPA-PMTXD, Rct 155 .cm2).Surprisingly, after a closer look at the obtained data, we found that the system containing no targeting agent (Au-MPA-PMTXD, Rct 1650 .cm2) interact with the cancer cells more strongly than those containing targeting agents (Au-MPA-PMTXD||Gln, Rct 130 .cm2), (Au-MPA-PMTXD||FOA, Rct 220 .cm2), and (Au-MPA-PMTXD||GlcN, Rct 690 .cm2).
As a final result, PMTXD, due to its unique antifolate structure and probably its very favorable orientation, interacts with cancer cells more effectively than the nanosystems having targeting agent in its vicinity. In other words, for the delivery of PMTXD to cancer cells via nanostructures and nanoparticles, it is likely that there will be no need to improve the delivery with the help of targeting agents. This research will pave the way for more comprehensive studies using nanoparticles through in-vivo and clinical experiments.
