Farklı Şekilli Nanopartiküllerin Geliştirilmesi, İmmünoterapötik ve Kemoterapötik Madde Yüklü Optimum Şekilli Nanopartiküllerin Küçük Hücreli Dışı Akciğer Kanseri Üzerine Antikanser Etkinliğinin Değerlendirilmesi

Abstract

Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. Cancer immunotherapy, offers new opportunities for the treatment of lethal lung cancer, immune checkpoint inhibitors used in the treatment of NSCLC have achieved a favorable response in only 15-25% of patients. TGF-β inhibitor galunisertib and the immune checkpoint inhibitor nivolumab were co-loaded into the nanosystem consisting of derivatives of FDA and EMA approved PLGA and the nanosystem was conjugated with anti-EGFR in the scope of Ph.D. thesis to improve efficiency of immunotherapy in treatment of NSCLC. In this study, in addition to spherical nanoparticles, rod and elliptical disk shaped nanoparticles were prepared by a modified film stretching method and the effects of shape on various parameters were investigated. Following in vitro and in vivo characterization of the nanoparticles, optimum particle shape was determined. In vitro characterization studies of the targeted spherical nanoparticles (optimum shape) were examined including their toxicity on healthy and tumor cells, T cell immune responses. Finally in vivo evaluation on tumor bearing mices were performed. Biodistribution studies have shown that the acumulation of antibody conjugated nanoparticles around the tumor was higher compared to the control group (p>0,05). As a result of in vivo experiments, it was determined that the co-loaded antibody conjugated nanoparticles are more effective in tumor shrinkage than non-targeted nanoparticles and they showed similar effects with the combined solution.