KANSER TEDAVİSİNDE KULLANILMAK ÜZERE İPEK PROTEİN NANOPARTİKÜLLERİN HAZIRLANMASI VE KARAKTERİZASYONU

Abstract

For the treatment of cancer in recent years, new generation methods are being developed by directly targeting of cancer cells, thereby preventing damage to healthy tissue. siRNA therapies are one of the new generation therapeutics; by acting directly at the level of problematic gene’s mRNA. However, due to its negative charge, siRNA cannot easily pass across the cell membrane so have several limitations such as inability to penetrate efficiently into cells. Also, because of the siRNA’s high possibility of enzymatic degradation by nucleases, their half-life is very short. An effective and suitable carrier system is needed for transportation of siRNA. Nanoparticles with appropriate sizes, are being frequently used as carriers to minimize the toxicity and to facilitate the RNA/DNA/therapeutics into the cells. FDA approved silk protein materials are being investigated for tissue engineering and cell culture with their not toxic, biodegradable, easy elimination from the body and stability properties. They are commonly used as drug delivery systems, also as a genetic material carrier as a non-viral system, due to their high transfection effects and resilience of the enzyme DNase. In this thesis, sericin and fibroin were interacted with albumin at various ratios and nine different nanoparticles were synthesized, optimized and characterized. siRNA binding was enhanced by decorating the nanoparticles with PLL (poly-l-lysine) and targeted nanoparticles against to larynx cancer cells were obtained by modifing them with hyaluronic acid (HA) as a ligand. Nanoparticles were loaded with CK2, ASH2L and Cyclin D1 targeting siRNAs and gene silencing efficiencies were investigated in HEp-2 cell line and mouse models. Obtained results demonstrated that PLL modified HA attached albumin:serisin (Alb:Ser) 2:1 w/w nanoparticles are better candidate for siRNA delivery among others due to their promising therapeutic potential in larynx cancer therapy.