Studies On Nanoparticle Assessed RNA Interference In Brain Tumor Cell Line U251

RNA interference is an effective gene silencing mechanism. This kind of short double-stranded RNA can degrade its target gene mRNA and lead to gene silencing. Now, RNAi based technology has been widely used in gene function research and proved an outstanding potentiality for gene therapy of many diseases. Among them cancers that well known to be able to affect most human body tissues causing serious health implications up to death. Glioma, brain cancer, is the most common tumor affecting human nervous system accounting for about40-50%of nervous system neoplasms. Since its growth is invasive, it is difficult to excise by surgery and the need for new and efficient non invasive therapies is pressing. Recentlly, nanomaterials have emerged as promising siRNA transferring vectors offering a new approach for siRNA based gene therapy of tumors.In this study, we first modify hydrophobic quantum dots (QDs) with amphiprotic ploymer PMAL-C8and further with a branched PEI (25KDa) which was conjugated to QD-PMAL through covalent cross-linking. The prepared fluorescent nanoparticles showed an excellent stability with positive surface charge in physiological solutions. siRNA transfection results show both the transfection efficacy and cell viability are better when the cell culture media containing serum. We observed the green fluorescence of free Alexaflour488siRNA released by the effect of PEI "proton sponge" in cytoplasm. Best gene silencing level reach when the assembly ratio of QD:siRNA is1:2. Transwell experiment and gene chips analysis show that the Glioma cell migration is related to the JAM2gene function, but the exact mechanism of this need more research.The overall results of this study present the importance of the nanoparticle-siRNA conjugates in tumor targeting and treatment using noninvasive gene therapeutics. The nanometer size of nanoparticles and their surface avability for modifications and conjugation combined with the efficient siliencing activity of siRNA are the core points behind the reported efficiency of these bioconjugates.