Studying the cell internalization pathways of PLGA nanoparticles and the derivatives obtained from its incorporation with carbohydrates

Cancer is a disease that cells lose control of division and have excessive division due to the mutations. These cells that reproduce uncontrollably begin to accumulate in the region where they are located. While using the nano carrier, better treatment results are obtained compared to traditional treatments. It is very important to enter the cell with the chemotherapy agent it carries in the nano carrier. In this thesis, it was investigated how the PLGA nano carrier which is prepared in the laboratory uptaken by cancerous cells due to the the fast metabolism of cancer cells. Thus, more effective treatments can be obtained by knowing more about the relationship between cellular uptake pathway and nano carriers. Although cancer cells find alternative energy sources in terms of nutrition, the major change is the changes in the glycolysis mechanism. Cancer cells want to quickly reach the source of glucose with the effect of Warburg. Using this request, PLGA (polylactic acid co glycolic acid), which will be used as a nano carrier system, is coated with cellulose and levan, which is a derivative of glucose and fructose, and introduced into the MCF-7 breast cancer cell environment. Thus, it is planned to increase the interest of MCF-7 breast cancer cells to PLGA nano carrier. In addition, the cellular uptake pathways of the nano carrier were examined by giving nano carrier and inhibitors together. With usage of inhibitors, clathrin independent endocytosis, macropinostosis and phagocytosis pathways are inhibited. There is a pharmacological or chemical inhibitor of the entry pathway available in the literature for each cell. For this purpose, MCF-7 breast cancer cells have been used. Since the PLGA nano carrier will be fluorescently labeled, it can be followed with a fluorescence microscope, detailed measurements were made with the ELISA device. Dimensional analysis of cellulose PLGA, levan PLGA, fluorescent PLGA and PLGA nano carriers were analyzed with DLS device and their loads with Zeta potential, and toxicity studies of inhibitors and nano carriers were checked with Sulforhodamine B viability test. All nano carrier systems are prepared by evaporation and precipitation method. The fluorescence labeled PLGA is covered with levan and cellulose, and its fluorescence labeled and unmarked PLGA nano carriers are prepared. Nontoxic doses of inhibitors and nano carriers were measured. Cells were first exposed to inhibitors, then treated with nano carriers. Cells that are not exposed to the inhibitor were used as a control. Inhibitors mostly affected the penetration of uncoated PLGA nano carriers into the cell. That suggests that the uncoated nano carrier could easily uptaken by the cells. In terms of PLGA coated with cellulose and PLGA coated with levan, chlorpromazine prevented the highest rate of entry into the cell, indicating that the coated nanocarriers use clathrin independent endocytosis for entry into the cell.