title: Preparation of novel curdlan nanoparticles for intracellular siRNA delivery.
abstract: RNA interference (RNAi) down-regulates gene expression post-transcriptionally, which is a therapeutically significant phenomenon that could potentially reduce the level of disease related proteins that are undruggable by conventional small molecular approaches. However, clinical application of small interference RNAs (siRNAs) requires design of potent siRNA sequences and development of safe and efficient delivery systems. To create a biocompatible siRNA delivery agent, we chemically modified natural polysaccharide curdlan in a regioselective manner to introduce amino group in the glucose units. The resulting 6-amino-curdlan (6AC) is water soluble and forms nanoparticles upon complexing with siRNAs. The novel curdlan-based nanoparticles efficiently delivered siRNAs to human cancer cells and mouse primary cells, and reduced 70-90% of target mRNA level. Moreover, 6AC nanoparticles delivered siRNA targeting eGFP to mouse embryonic stem (mES) cells stably expressing eGFP, and produced substantial reductions of GFP protein level. The novel curdlan-based nanoparticle is a promising vehicle for delivery of short RNAs to knock down endogenous mRNAs.
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia, 010020, PR China.
authors.forename: Jingfen
authors.initials: J
authors.lastname: Han
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia, 010020, 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, 010020, PR China.
authors.forename: Wuyinga
authors.initials: W
authors.lastname: Borjihan
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia, 010020, PR China.
authors.forename: Tsogzolmaa
authors.initials: T
authors.lastname: Ganbold
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Pediatrics, Rady Children's Hospital San Diego and University of California San Diego, La Jolla, CA 92093, USA. Electronic address: trana@sanfordburnham.org.
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
authors.affiliation: School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia, 010020, PR China; Program for RNA Biology, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: hbaigude@imu.edu.cn.
authors.forename: Huricha
authors.initials: H
authors.lastname: Baigude
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D053595:Embryonic Stem Cells / Q000187:drug effects; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D047071:beta-Glucans / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering; D047071:beta-Glucans; C038459:curdlan
keywords: Cancer cells; Curdlan; Nanoparticles; RT-qPCR; siRNA delivery