Dodekahidro-kloso-dodekaborat yüklü polimer miseller içeren çok katmanlı kapsüllerin hazırlanması

Boron Neutron Capture Therapy (BNCT) is a non-invasive radiotherapy technique which is based on delivery of non-radioactive 10B compounds to cancer cells and irradiation of the tumour tissues with low energy thermal neutrons. It is a promising radiotherapy technique due to reduce the side effects of the treatment. The main goal of this thesis is to prepare a non-toxic polymer vehicle to provide efficient delivery of 10B to cancer cells. Dodecahydro-closo-dodecaborate (B12H12)2- (B12) anion was utilized as a model 10B containing agent because of its high boron concentration. Quaternized poly(2-vinyl pyridine)-b-poly(ethylene oxide) (QP2VPb-PEO) was chosen as a model neutral-cationic block copolymer to construct the carrier. The electrostatic association between QP2VP and B12 induced selfassembly of QP2VP-b-PEO, resulting in micelles with (B12+QP2VP)-core and PEO-corona. (B12+QP2VP)-b-PEO micelles were found to be not stable against dilution in biological medium. Layer-by-Layer (LbL) deposition technique was used to self-assemble these micelles onto colloidal CaCO3 microparticles to enhance their stability. Tannic acid (TA) was used to drive the LbL assembly through hydrogen bonding interactions between hydrogen accepting PEO-corona and hydrogen donating TA. Stability of LbL capsules in biological medium was assured by construction of barrier layers composed of poly(N-vinyl-caprolactam) (PVCL) and TA on top of (B12+QP2VP)- b-PEO micelles and TA multilayers. Cytotoxicity and cellular association of LbL capsules was assessed in non-hollow and hollow form using Hep G2 cell line. Capsules were found to show no systematic cytotoxicity on Hep G2 cell line. Cellular association studies and boron concentrations determined through inductively coupled plasma optical emission spectroscopy (ICP-OES) showed that both non-hollow and hollow capsules associated with Hep G2 cells and delivered boron to the cells. Overall, this study generated fundamental knowledge on B12 induced micellization and stabilization of micelles in biological medium. These findings may form a basis to develop polymer carriers for boron delivery for BNCT. Keywords: Self-assembly, Layer-by-Layer Self-assembly Technique, Boron Neutron Capture Therapy, Microcapsules