S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dental Science(치의과학과) Theses (Master's Degree_치의과학과)
Receptor meditated endocytosis of hyper osmotic folate conjugated poly-sorbitol mediated transporter with siOPA1 for lung cancer therapy
폐암 치료를 위한 엽산-삼투성의 폴리솔비톨계 siOPA1 전달체의 수용체 매개 세포내 이동
- Rohidas B. Arote
- 치의학대학원 치의과학과
- Issue Date
- 서울대학교 대학원
- Gene delivery; sorbitol; PEI; Folate; receptor-mediated endocytosis; lung cancer; cancer therapy
- 학위논문 (석사)-- 서울대학교 대학원 : 치의과학과 분자유전학전공, 2016. 8. Rohidas B. Arote.
- Lung cancer is one of the mostly deadly in the world, represents a therapeutic problem. Although therapeutics for cancer such as chemotherapy, immunotherapy and radio therapy, it shown considerable side effects. Once patients received therapy, the death rate for lung cancers is significantly high. To overcome such a common therapies, nanoparticle-mediated siRNA delivery strategies expect a latent way of approach using selective silencing effect and non-viral vectors for reducing the cytotoxicity. In this paper, folate (FA) moiety as ligand conjugated poly(sorbitol-co-PEI) (FPS) based gene transporter was designed by composing of low molecular polyethylenimine (LMW PEI) and D-sorbitol with FA. Folate receptor frequently overexpressed on the various cancer cells, and that means folate conjugated nanoparticle can be effectively transported to selective cancer cells as ideal strategy for improved gene therapy.
Additionally, We used the siOPA1 that have apoptosis effect through mitochondria fusion. OPA1 protein level stability is significantly improtant for maintaining normal mitochondria cristae structure and function, for conservation of the inner membrane structure and for protecting cells from apoptosis. Consequently, FPS/siOPA1 indicated high cell viability, increased cellular uptake ability, to lung cancer targeting in-vitro as well as in-vivo.