Radyoterapide Kullanılmak Üzere Kuantum Noktaları ve Fotoduyarlaştırıcı İçeren Tümöre Spesifik Nanoboyutlu Lipozomların Geliştirilmesi

Abstract

Cancer is the second most common cause of death in the world. Common approaches in cancer treatment include surgery, radiotherapy, chemotherapy, hormone therapy, immune therapy, and targeted therapy. In radiotherapy, which causing lethal damage in cancer cells by using ionizing radiation, various approaches are tried to increase the biological effect without increasing the applied radiation dose. Radiosensitizers can be applied before, during or after radiotherapy and make cells more sensitive to radiation. In recent years, number of studies have been performed on nanotechnology-based radiosensitizers such as metal nanoparticles (Au, Ag), quantum dots (QDs), super paramagnetic iron oxide and non-metal nanoparticles (silicon, fulleren). This method is called as "Nanoparticle Enhanced X-ray Therapy = NEXT". In addition, the use of scintillating or continuously luminescent nanoparticles such as QDs with photoensitizers is a new field of study. In this study, it is intended to develope liposomal radiosensitizer which is quantum dots -Chlorine e6 conjugate encapsulated, PEG-coated, nanoscale and surface modified with folic acid. By this way, it is aimed to provide more benefit and to destroy tumor cells by using lower radiation dose compared to clinically used X-ray doses. Characterization studies have shown that liposomes have appropriate encapsulation efficiency and particle size. The cytotoxicity of liposome formulations on 4T1 (mouse breast cancer) tumor cell lines were examined. It was observed that there is 27,11,73 % increase in cell death when it is compared with the effect of only 5 Gy X-ray radiation dose was compared with the administration of liposome formulation following by 5 Gy X-ray radiation dose. The antitumor efficacy of the liposomal radiosensitizer containing the QD-Ce6 conjugate was investigated in mice having in vivo tumor model. In this context, weight changes in mice, changes in tumor volume, survival times were monitored and pathological and histological evaluations were made on tumor tissue and other organs. The obtained results showed that DSPCL-FA-K liposome dispersion (QD-Ce6 conjugate containing formulation which has DSPC:Chol:SA:PEG2000-DSPE:FA-PEG2000-DSPE lipid composition) prepared in this thesis scopes might be a promising radiosensitizing agent to achieve the same or better efficacy in treatment by applying less radiation dose in radiotherapy.