title: PEGylation of 6-amino-6-deoxy-curdlan for efficient in vivo siRNA delivery.
abstract: RNA interference (RNAi) is an evolutionarily conserved gene-silencing phenomenon that shows great promise for developing new therapies. However, the development of small interfering RNA (siRNA)-based therapies need to establish efficient delivery system that silences target genes with siRNA doses that is clinically feasible in humans. Here we report synthesis and in vivo study of a novel PEGylated curdlan-based nanoparticle, designated as 6AC-100PEG, obtained by conjugation of mPEG 2000 to 6-amino-6-deoxy-curdlan. The complex of siRNA/6AC-100PEG showed homogenous nanoparticles with an average diameter of 200nm. MTT assay indicated that 6AC-100PEG does not have apparent cytotoxicity. Systemic administration of a complex of siapoB/6AC-100PEG significantly reduced the level of apoB mRNA in mouse liver, indicating that 6AC-100PEG can efficiently deliver siRNA to mouse liver and induce RNAi. Administration of siRNA/6AC-100PEG to mouse did not elevate liver enzyme level in the serum, indicating that 6AC-100PEG nanoparticle is a promising in vivo siRNA delivery agent.
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia 010021 PR China.
authors.forename: Altanzul
authors.initials: A
authors.lastname: Altangerel
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia 010021 PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cai
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia 010021 PR China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia 010021 PR China.
authors.forename: Yinga
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia 010021 PR China. Electronic address: hbaigude@imu.edu.cn.
authors.forename: Huricha
authors.initials: H
authors.lastname: Baigude
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia 010021 PR China. Electronic address: hanjingfen@imu.edu.cn.
authors.forename: Jingfen
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000009:adverse effects / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014018:Tissue Distribution; D047071:beta-Glucans / Q000737:chemistry*
chemical_list: D001055:Apolipoproteins B; D053769:Nanocapsules; D034741:RNA, Small Interfering; D047071:beta-Glucans; D011092:Polyethylene Glycols; C038459:curdlan
keywords: Biodistribution; Curdlan; Nanoparticle; PEG; siRNA delivery