Cell Type-Specific Delivery of RNAi by Ligand-Functionalized Curdlan Nanoparticles: Balancing the Receptor Mediation and the Charge Motivation.
Tissue-specific delivery of therapeutic RNAi has great potential for clinical applications. Receptor-mediated endocytosis plays a crucial role in targeted delivery of biotherapeutics including short interfering RNA (siRNA). Previously we reported a novel Curdlan-based nanoparticle for intracellular delivery of siRNA. Here we designed a nanoparticle based on ligand-functionalized Curdlan. Disaccharides were site-specifically conjugated to 6-deoxy-6-amino Curdlan, and the cell line specificity, cellular uptake, cytotoxicity, and siRNA delivery efficiency of the corresponding disaccharide-modified 6-deoxy-6-amino-Curdlan were investigated. Observation by fluorescence microscopy as well as flow cytometry showed that galactose-containing Curdlan derivatives delivered fluorescently labeled short nucleic acid to HepG2 cells expressing ASGPR receptor but not in other cells lacking surface ASGPR protein. Moreover, highly galactose-substituted Curdlan derivatives delivered siRNA specifically to ASGPR-expressing cells and induced RNAi activities, silencing endogenous GAPDH gene expression. Our data demonstrated that galactose-functionalized 6-deoxy-6-amino-Curdlan is a promising carrier for short therapeutic nucleic acids for clinical applications.
School of Chemistry & Chemical Engineering, Inner Mongolia University , 235 West College Road, Hohhot, Inner Mongolia 010020, P. R. China.
Yinga
Y
Wu
School of Chemistry & Chemical Engineering, Inner Mongolia University , 235 West College Road, Hohhot, Inner Mongolia 010020, P. R. China.
Jia
J
Cai
School of Chemistry & Chemical Engineering, Inner Mongolia University , 235 West College Road, Hohhot, Inner Mongolia 010020, P. R. China.
Jingfen
J
Han
School of Chemistry & Chemical Engineering, Inner Mongolia University , 235 West College Road, Hohhot, Inner Mongolia 010020, P. R. China.
Huricha
H
Baigude
D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D002021:Buffers; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D016923:Cell Death; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D055672:Static Electricity; D047071:beta-Glucans / Q000737:chemistry* / Q000633:toxicity
D037263:Asialoglycoprotein Receptor; D002021:Buffers; D008024:Ligands; D034741:RNA, Small Interfering; D047071:beta-Glucans; C038459:curdlan
ASGPR; Curdlan; galactose; receptor-mediated delivery; siRNA delivery