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

Nanoscale
Jingguo LiXintao Shuai

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....Continue Reading

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Citations

May 13, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yinjian ZhouWei Liang
Jan 7, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Ping WangXintao Shuai
Sep 24, 2014·ACS Applied Materials & Interfaces·Yu ZhaoFu-Jian Xu
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Sep 22, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Khan MuhammadYakai Feng
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Apr 24, 2017·Polymers·Ansuja Pulickal MathewIn-Kyu Park
Mar 16, 2017·Topics in Current Chemistry·Hu-Lin JiangChong-Su Cho
Oct 10, 2020·Frontiers in Chemistry·Huayang FengJingguo Li
Aug 14, 2020·Molecular Pharmaceutics·Ester J KwonSangeeta N Bhatia
Apr 1, 2021·Journal of Biomedical Nanotechnology·Liuqi ShiJingguo Li
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shuang LiuDu Cheng
Nov 2, 2018·Bioconjugate Chemistry·Jie ChenXuesi Chen
Jun 23, 2020·Biomacromolecules·Raut BholakantWei Chen

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