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  • Title: Amphiphilic gold nanoparticles displaying flexible bifurcated ligands as a carrier for siRNA delivery into the cell cytosol.
    Author: Niikura K, Kobayashi K, Takeuchi C, Fujitani N, Takahara S, Ninomiya T, Hagiwara K, Mitomo H, Ito Y, Osada Y, Ijiro K.
    Journal: ACS Appl Mater Interfaces; 2014 Dec 24; 6(24):22146-54. PubMed ID: 25466488.
    Abstract:
    The nanoparticle-based delivery of siRNA with a noncationic outermost surface at a low particle concentration is greatly desired. We newly synthesized a bifurcated ligand (BL) possessing hydrophobic and hydrophilic arms as a surface ligand for gold nanoparticles (AuNPs) to allow siRNA delivery. The concept underlying the design of this ligand is that amphiphilic property should allow AuNPs to permeate the cell cytosol thorough the endosomal membrane. BLs and quaternary cationic ligands were codisplayed on 40 nm AuNPs, which were subsequently coated with siRNA via electrostatic interaction. The number of siRNAs immobilized on a single nanoparticle was 26, and the conjugate showed a negative zeta potential due to siRNAs on the outermost surface of the AuNPs. Apparent gene silencing of luciferase expression in HeLa cells was achieved at an AuNP concentration as low as 60 pM. Almost no gene silencing was observed for AuNPs not displaying BLs. To reveal the effect of the BL, we compared the number of AuNPs internalized into HeLa cells and the localization in the cytosol between AuNPs displaying and those not displaying BLs. These analyses indicated that the role of BLs is not only the simple promotion of cellular uptake but also involves the enhancement of AuNPs permeation into the cytosol from the endosomes, leading to effective gene silencing.
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