%0 Journal Article
%T Hepatocyte-targeting gene transfer mediated by galactosylated poly(ethylene glycol)- graft-polyethylenimine derivative
%A Wang YQ
%A Su J
%A Cai WW
%A Lu P
%A Yuan LF
%A Jin T
%A Chen SY
%A Sheng J
%J Drug Design, Development and Therapy
%D 2013
%I Dove Medical Press
%R http://dx.doi.org/10.2147/DDDT.S42582
%X tocyte-targeting gene transfer mediated by galactosylated poly(ethylene glycol)- graft-polyethylenimine derivative Original Research (86) Total Article Views Authors: Wang YQ, Su J, Cai WW, Lu P, Yuan LF, Jin T, Chen SY, Sheng J Published Date March 2013 Volume 2013:7 Pages 211 - 221 DOI: http://dx.doi.org/10.2147/DDDT.S42582 Received: 09 January 2013 Accepted: 21 February 2013 Published: 26 March 2013 Yuqiang Wang,1,* Jing Su,2,* Wenwei Cai,3 Ping Lu,3 Lifen Yuan,3 Tuo Jin,2 Shuyan Chen,1 Jing Sheng3 1Department of Geriatrics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People¡¯s Republic of China; 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People¡¯s Republic of China; 3Department of Geriatrics, Shanghai Ninth People¡¯s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People¡¯s Republic of China *Both authors contributed equally to this work 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¨C100 nm and zeta potential was 6¨C15 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¨C65 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.
%K gene delivery
%K hepatocyte targeting
%K galactose
%K cytotoxicity
%K transfection efficiency
%U https://www.dovepress.com/hepatocyte-targeting-gene-transfer-mediated-by-galactosylated-polyethy-peer-reviewed-article-DDDT