Jump to main content
Jump to site search

Issue 3, 2014
Previous Article Next Article

Copolymer of poly(ethylene glycol) and poly(l-lysine) grafting polyethylenimine through a reducible disulfide linkage for siRNA delivery

Author affiliations

Abstract

siRNA therapy research has primarily focused on the synthesis and development of effective siRNA delivery vectors with easy biodegradability and low toxicity. In the present study, we synthesized a ternary copolymer mPEG-b-PLL-g-(ss-lPEI), denoted as PLI, by introducing disulfide bond linkages to graft low molecular weight linear polyethylenimine (lPEI) to the block copolymer of poly(L-lysine) (PLL) and poly(ethylene glycol) (PEG) for siRNA delivery. The PLL block and disulfide linkage rendered the carrier biodegradability, while lPEI grafting brought about the proton buffering capacity for lysosomal siRNA release and low cationic toxicity. Conjugation of a single chain monoclonal antibody (Herceptin) to the carrier as a targeting ligand for the Her2/neu receptor significantly increased the transfection activity of the copolymer/siRNA nanocomplex (i.e. the polyplex) in Skov-3, a human ovarian cancer cell line. Determination of gene expression at both the mRNA and protein levels demonstrated that Her2-targeted delivery of siRNA (XIAP siRNA) effectively downregulated the targeted XIAP (X-linked inhibitor of apoptosis protein) gene, resulting in enhanced cancer cell apoptosis and improved therapeutic efficacy in vitro and in vivo. The distinct features of low cytotoxicity, easy degradability, and high siRNA transfection efficiency make the copolymer a promising candidate for siRNA therapy in tumors.

Graphical abstract: Copolymer of poly(ethylene glycol) and poly(l-lysine) grafting polyethylenimine through a reducible disulfide linkage for siRNA delivery

Back to tab navigation

Supplementary files

Publication details

The article was received on 19 Sep 2013, accepted on 20 Nov 2013 and first published on 26 Nov 2013


Article type: Paper
DOI: 10.1039/C3NR05024F
Nanoscale, 2014,6, 1732-1740

  •   Request permissions

    Copolymer of poly(ethylene glycol) and poly(L-lysine) grafting polyethylenimine through a reducible disulfide linkage for siRNA delivery

    J. Li, D. Cheng, T. Yin, W. Chen, Y. Lin, J. Chen, R. Li and X. Shuai, Nanoscale, 2014, 6, 1732
    DOI: 10.1039/C3NR05024F

Search articles by author

Spotlight

Advertisements