İmmünokemoterapötik Nanoplekslerin Kolon Kanseri Tedavisinde Etkinlik ve Güvenliliğinin İn Vitro-İn Vivo Değerlendirilmesi

Abstract

Chemotherapy is the most commonly used method after surgery in the treatment of colon cancer. However, cancer cells escape the recognition mechanism of immune system cells in to survive, developing resistance to chemotherapeutics with their differentiation abilities. Therefore, it is believed that the use of immunotherapy in combination with chemotherapy can increase the effectiveness of the treatment. Nanoplexes were formed based on opposite charge interaction of macromolecules as the nanocarrier system in this study and cyclodextrin (CD) polymer, 5-Fluorouracil (5-FU) and Interleukin-2 (IL-2) were used to obtain nanoplexes. Mean particle size, particle size distribution, surface charge, drug loading capacity, drug release profile and stability of nanoplexes were analysed. Safety of CD polymers was determined with cell culture. Then, the anticancer activities of the drug-loaded nanoplexes were determined by 2-dimensional cell culture and real-time cell viability. With 3-dimensional tumor culture studies that can reflect the microenvironment of the tumor in vitro, the efficiency of nanoplexes was determined by cell viability, immunohistochemical examination and electron microscopy examination. The in vivo safety of CD polymers was determined by blood samples obtained after a single dose intravenous (i.v.) administration in healthy mice. Finally, in tumor-induced mice, the antitumoral activities of nanoplexes were determined in terms of survival rate, metastasis and immune response parameters. As a result of the studies, nanoplexes carrying IL-2 and 5-FU together were prepared and a promising model drug delivery system was presented for future applications of parenteral colorectal immunochemotherapy.