Receptor meditated endocytosis of hyper osmotic folate conjugated poly-sorbitol mediated transporter with siOPA1 for lung cancer therapy

Abstract

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.