title: Target-specific gene silencing of layer-by-layer assembled gold-cysteamine/siRNA/PEI/HA nanocomplex.
abstract: Target-specific intracellular delivery of small interfering RNA (siRNA) is regarded as one of the most important technologies for the development of siRNA therapeutics. In this work, a cysteamine modified gold nanoparticles (AuCM)/siRNA/polyethyleneimine (PEI)/hyaluronic acid (HA) complex was successfully developed using a layer-by-layer method for target-specific intracellular delivery of siRNA by HA receptor mediated endocytosis. Atomic force microscopic and zeta potential analyses confirmed the formation of a AuCM/siRNA/PEI/HA complex having a particle size of ca. 37.3 nm and a negative surface charge of ca. -12 mV. With a negligible cytotoxicity, AuCM/siRNA/PEI/HA complex showed an excellent target-specific gene silencing efficiency of ca. 70% in the presence of 50 vol % serum, which was statistically much higher than that of siRNA/Lipofectamine 2000 complex. In the competitive binding tests with free HA, dark-field bioimaging and inductively coupled plasma-atomic emission spectroscopy confirmed the target-specific intracellular delivery of AuCM/siRNA/PEI/HA complex to B16F1 cells with HA receptors. Moreover, the systemic delivery of AuCM/siRNA/PEI/HA complex using apolipoprotein B (ApoB) siRNA as a model drug resulted in a significantly reduced ApoB mRNA level in the liver tissue. Taken together, AuCM/siRNA/PEI/HA complex was thought to be developed as target-specific siRNA therapeutics for the systemic treatment of various liver diseases.
authors: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Korea.
authors: Min-Young
authors: MY
authors: Lee
authors: Sang-Jun
authors: SJ
authors: Park
authors: Kitae
authors: K
authors: Park
authors: Ki Su
authors: KS
authors: Kim
authors: Hwiwon
authors: H
authors: Lee
authors: Sei Kwang
authors: SK
authors: Hahn
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000172:deficiency / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D003543:Cysteamine / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004705:Endocytosis; D020868:Gene Silencing; D006046:Gold / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D042541:Intracellular Space / Q000378:metabolism; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D057054:Molecular Imaging; D049329:Nanostructures / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics
chemical_list: D001055:Apolipoproteins B; D004337:Drug Carriers; D034741:RNA, Small Interfering; D003543:Cysteamine; D006046:Gold; D011094:Polyethyleneimine; D006820:Hyaluronic Acid