An Improvement Delivery of siRNA by IRQ Ligand-Modified Double Membranous Nano-Carrier

摘要

In the present study, the enhancement of siRNA delivery into cytosol from the IRQ-modified multi-envelope type nano-device (IRQ-MEND) was investigated. It is known that IRQ-MEND efficiently enters cells by clathrin-mediated endocytosis and caveolar endocytosis pathways, resulting in gene silencing. In the present study, we controlled the number of layers of IRQ-MEND encapsulating siRNA by using double membranous nano-device strategy. This vector design overcomes intracellular barriers such as endosomal membrane, resulting drastically enhance transgene expression. In addition, the contribution of uptake mechanism of IRQ-modified nano-carrier to transgene expression was studied. The use of hypertonic treatment inhibited gene silencing, but it was not suppressed by the addition of filipin. These results indicate that low pH is important to induce the transgene expression. In conclusion, delivery of cytosolic siRNA can be enhanced by the use of double-membranous nano-carrier system which utilizes a clathrin-mediated endocytosis pathway to induce gene silencing.