title: Hepatocyte-targeting gene transfer mediated by galactosylated poly(ethylene glycol)-graft-polyethylenimine derivative.
abstract: Biscarbamate cross-linked polyethylenimine derivative (PEI-Et) has been reported as a novel nonviral vector for efficient and safe gene transfer in our previous work. However, it had no cell-specificity. To achieve specific delivery of genes to hepatocytes, galactosylated poly(ethylene glycol)-graft-polyethylenimine derivative (GPE) was prepared through modification of PEI-Et with poly(ethylene glycol) and lactobionic acid, bearing a galactose group as a hepatocyte-targeting moiety. The composition of GPE was characterized by proton nuclear magnetic resonance. The weight-average molecular weight of GPE measured with a gel permeation chromatography instrument was 9489 Da, with a polydispersity of 1.44. GPE could effectively condense plasmid DNA (pDNA) into nanoparticles. Gel retardation assay showed that GPE/pDNA complexes were completely formed at weigh ratios (w/w) over 3. The particle size of GPE/pDNA complexes was 79-100 nm and zeta potential was 6-15 mV, values which were appropriate for cellular uptake. The morphology of GPE/pDNA complexes under atomic force microscopy appeared spherical and uniform in size, with diameters of 53-65 nm. GPE displayed much higher transfection efficiency than commercially available PEI 25 kDa in BRL-3A cell lines. Importantly, GPE showed good hepatocyte specificity. Also, the polymer exhibited significantly lower cytotoxicity compared to PEI 25 kDa at the same concentration or weight ratio in BRL-3A cell lines. To sum up, our results indicated that GPE might carry great potential in safe and efficient hepatocyte-targeting gene delivery.
authors.affiliation: Department of Geriatrics, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Wenwei
authors.initials: W
authors.lastname: Cai
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Lifen
authors.initials: L
authors.lastname: Yuan
authors.forename: Tuo
authors.initials: T
authors.lastname: Jin
authors.forename: Shuyan
authors.initials: S
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Sheng
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D024202:Electrophoretic Mobility Shift Assay; D005690:Galactose / Q000009:adverse effects / Q000737:chemistry; D018014:Gene Transfer Techniques / Q000009:adverse effects; D006367:HeLa Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D008970:Molecular Weight; D053758:Nanoparticles; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry; D011094:Polyethyleneimine / Q000009:adverse effects / Q000737:chemistry; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry; D051381:Rats; D014162:Transfection
chemical_list: D011108:Polymers; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D005690:Galactose
keywords: cytotoxicity; galactose; gene delivery; hepatocyte targeting; transfection efficiency