title: Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma.
abstract: Lactosylated gramicidin-containing lipid nanoparticles (Lac-GLN) were developed for delivery of anti-microRNA-155 (anti-miR-155) to hepatocellular carcinoma (HCC) cells. MiR-155 is an oncomiR frequently elevated in HCC. The Lac-GLN formulation contained N-lactobionyl-dioleoyl phosphatidylethanolamine (Lac-DOPE), a ligand for the asialoglycoprotein receptor (ASGR), and an antibiotic peptide gramicidin A. The nanoparticles exhibited a mean particle diameter of 73 nm, zeta potential of +3.5mV, anti-miR encapsulation efficiency of 88%, and excellent colloidal stability at 4°C. Lac-GLN effectively delivered anti-miR-155 to HCC cells with a 16.1- and 4.1-fold up-regulation of miR-155 targets C/EBPβ and FOXP3 genes, respectively, and exhibited significant greater efficiency over Lipofectamine 2000. In mice, intravenous injection of Lac-GLN containing Cy3-anti-miR-155 led to preferential accumulation of the anti-miR-155 in hepatocytes. Intravenous administration of 1.5 mg/kg anti-miR-155 loaded Lac-GLN resulted in up-regulation of C/EBPβ and FOXP3 by 6.9- and 2.2-fold, respectively. These results suggest potential application of Lac-GLN as a liver-specific delivery vehicle for anti-miR therapy.
authors.affiliation: Molecular, Cellular and Developmental Biology Program, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Mengzi
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Bryant C
authors.initials: BC
authors.lastname: Yung
authors.forename: Ly J
authors.initials: LJ
authors.lastname: Lee
authors.forename: Kalpana
authors.initials: K
authors.lastname: Ghoshal
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D000906:Antibodies / Q000008:administration & dosage* / Q000737:chemistry; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002232:Carbocyanines / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry; D051858:Forkhead Transcription Factors / Q000235:genetics; D006096:Gramicidin / Q000008:administration & dosage* / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D007785:Lactose / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000276:immunology*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D000906:Antibodies; D022762:CCAAT-Enhancer-Binding Proteins; D002232:Carbocyanines; D004337:Drug Carriers; D005456:Fluorescent Dyes; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008055:Lipids; D035683:MicroRNAs; C089187:cyanine dye 3; D006096:Gramicidin; D007785:Lactose