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

Content Provider	Royal Society of Chemistry (RSC)
Author	Yin, Tinghui Cheng, Du Shuai, Xintao Chen, Jifeng Chen, Weicai Li, Ruitang Li, Jingguo Lin, Yujie
Copyright Year	2014
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.
Starting Page	1732
Ending Page	1740
Page Count	9
File Format	HTM / HTML PDF
ISSN	20403364
Volume Number	6
Issue Number	3
Journal	Nanoscale
DOI	10.1039/c3nr05024f
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Ethylene glycol Estrogen receptor Ligand Neu! X chromosome Small interfering RNA Enzyme inhibitor XIAP Cytotoxicity Monoclonal antibody PLI Protein Ovarian cancer Polyethylenimine Transfection Messenger RNA Gene Lysine Disulfide Copolymer Trastuzumab Apoptosis Cancer
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology

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