GÖZENEKLİ VE İÇİ BOŞ NANOYAPI FORMUNDA SiO2 TABANLI SİNERJİSTİK TERAPİ AJANLARININ GELİŞTİRİLMESİ VE İN-VİTRO TERAPİ PERFORMANSLARININ BELİRLENMESİ

Abstract

In this thesis, a SiO2 based multifunctional nanoparticle was developed for cancer treatment by utilizing photodynamic, photothermal and starvation therapies. Hollow, mesoporous and monodisperse silica nanoparticles (H-SiO2) were synthesized by using a multistep shape-templating sol-gel method to be used as a synergistic therapy agent. The nanoparticles were coated with polydopamine to give them the ability to produce photothermal effect. Thus, tumor cells were killed due to the temperature increase of up to 52°C generated in the tumor microenvironment by near-infrared laser irradiation at 808 nm. To create the photodynamic therapy function, chlorine e6, a photosensitizer, was immobilized on the polydopamine layer formed on the nanocarrier. Activated under 650 nm LED light, the nanoparticles caused oxidative damage to tumor cells by producing 1O2 reactive leading to cell death. The nanoparticles were then loaded with a cascade enzyme system including glucose oxidase (GOx) and catalase (CAT) enzymes. GOx induced starvation therapy by consuming glucose resources required for tumor cell metabolism, and the H2O2 produced because of glucose oxidation was converted to oxygen by CAT, enhancing photodynamic therapy efficacy. In-vitro studies showed that the synthesized synergistic therapy agent significantly increased cell death by photothermal, photodynamic and starvation therapies applied in T98G glioblastoma cells. The combined treatments reduced cell viability to 21% without the use of conventional antitumor agents. In this thesis, it was concluded that the synthesized H-SiO2@PDA@PDA@Ce6@GOx@CAT nanoparticles can be used as an effective synergistic therapy agent for cancer treatment.