İrinotekan ve stat3 inhibitörü yüklü plgapeg nanopartiküllerinin küçük hücreli akciğer kanserine aktif hedeflendirilmesi ve in vivo-in vitro değerlendirilmesi

Abstract

Small cell lung cancer accounts for 13-15% of all lung cancer cases. It spreads rapidly and has significant metastasis potential thus it is difficult to cure. In the concept of this thesis, polymeric nanoparticles actively targeted to tumor were developed to improve treatment efficiency and success in small cell lung cancer. Here, irinotecan, which is an anticancer agent that inhibits the topoisomerase I enzyme and Stattic, which is a Signal Transducer and Activator of Transcription-3 inhibitor were encapsulated into the formulated nanoparticles. In order to target the nanoparticles to the tumor, the antibody or antibody fragment of the CD56 receptor, which is highly expressed in small cell lung cancer cells, was conjugated to the nanoparticles and formulated nanoparticles were characterized. After formulation optimization and in vitro characterization studies, the optimum formulation was evaluated in terms of ex vivo biodistribution, in vivo hematotoxicity, in vivo antitumor efficacy and in vivo signal pathway inhibition. As a result of biodistribution studies, it was seen that the accumulation of antibody conjugated nanoparticles in the tumor tissue was significantly higher than the control group. in the tumor tissue (p<0,05). The highest reduction in tumor size was achieved with combined solution or co-loaded actively targeted nanoparticle treated groups. In conclusion, the combination of irinotecan and Stattic may be evaluated as a promising approach in SCLC therapy.