Royal College of Surgeons in Ireland
RGD-decorated cholesterol stabilized polyplexes for targeted siRN.pdf (1.58 MB)

RGD-decorated cholesterol stabilized polyplexes for targeted siRNA delivery to glioblastoma cells.

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Version 2 2021-12-03, 11:32
Version 1 2019-11-22, 16:55
journal contribution
posted on 2021-12-03, 11:32 authored by Bo Lou, Kate Connor, Kieron SweeneyKieron Sweeney, Ian Miller, Alice O'FarrellAlice O'Farrell, Eduardo Ruiz-Hernandez, David M. Murray, Garry P. Duffy, Alan Wolfe, Enrico Mastrobattista, Annette ByrneAnnette Byrne, Wim E. Hennink

The development of an effective and safe treatment for glioblastoma (GBM) represents a significant challenge in oncology today. Downregulation of key mediators of cell signal transduction by RNA interference is considered a promising treatment strategy but requires efficient, intracellular delivery of siRNA into GBM tumor cells. Here, we describe novel polymeric siRNA nanocarriers functionalized with cRGD peptide that mediates targeted and efficient reporter gene silencing in U87R invasive human GBM cells. The polymer was synthesized via RAFT copolymerization of N-(2-hydroxypropyl)-methacrylamide (HPMA) and N-acryloxysuccinimide (NAS), followed by post-polymerization modification with cholesterol for stabilization, cationic amines for siRNA complexation, and azides for copper-free click chemistry. The novel resultant cationic polymer harboring a terminal cholesterol group, self-assembled with siRNA to yield nanosized polyplexes (~ 40 nm) with good colloidal stability at physiological ionic strength. Post-modification of the preformed polyplexes with PEG-cRGD end-functionalized with bicyclo[6.1.0]nonyne (BCN) group resulted in enhanced cell uptake and increased luciferase gene silencing in U87R cells, compared to polyplexes lacking cRGD-targeting groups.


China Scholarship Council (CSC). ScienceFoundation Ireland Technology Innovation Award (15/TIDA/2963). BGLIOTRAIN^ (http://www.gliotrain. eu) award, a Horizon 2020 Research and Innovation program funded under the Marie Skłodowska-Curie ETN initiative (Grant Agreement #766069).



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Published Citation

Lou B, Connor K, Sweeney K, Miller IS, O'Farrell A, Ruiz-Hernandez E, Murray DM, Duffy GP, Wolfe A, Mastrobattista E, Byrne AT, Hennink WE. RGD-decorated cholesterol stabilized polyplexes for targeted siRNA delivery to glioblastoma cells. Drug Delivery and Translational Research. 2019:1-15

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  • Beaumont Hospital
  • Physiology and Medical Physics