Systemic in vivo delivery of siRNA to tumours using combination of polyethyleneimine and transferrin-polyethyleneimine conjugates

Biomaterials Science
Anna M GrabowskaCameron Alexander

Abstract

Materials for delivery of oligonucleotides need to be simple to produce yet effective in vivo to be considered for clinical applications. Formulations of biomaterials based on combinations of existing demonstrated polymeric gene carriers with targeted derivatives are potential candidates for rapid translation but have not been fully explored for siRNA applications. Here we investigated formulations based on derivatised PEI for delivery of siRNA to gastrointestinal cancer cells. siRNA was complexed with linear PEI alone or with a mixture of linear PEI and transferrin-conjugated branched PEI (TfPEI), and knockdown of reporter genes was investigated. Overall, the in vitro use of complexes containing TfPEI resulted in up to 93% knockdown at 72 h post-transfection. Sustained knockdown was also achieved in a bioluminescent xenograft model. When complexes were delivered intratumorally, a 43% reduction in luminescence was achieved in the treated group compared with the control group 48 h after treatment. For systemic administration, only the intraperitoneal route, and not the intravenous route was effective, with 49% knockdown achieved at 72 h and sustained up to 144 h (44%) after a single administration of TfPEI-complexed siRNA. No to...Continue Reading

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Citations

Dec 10, 2016·Biomaterials Science·Jingchao LiGuoping Chen
Feb 25, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Amy E ArnoldMolly Shoichet
Jan 8, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kaimin CaiJianjun Cheng
May 26, 2016·Biomaterials Science·Wenzhen LiaoYong Wang
Oct 21, 2016·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Wanwan ShenYiyun Cheng
Jul 13, 2018·Biomedical Microdevices·Daniel F Costa, Vladimir P Torchilin
Jun 23, 2020·Biomacromolecules·Raut BholakantWei Chen

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