Phosphonium polymethacrylates for siRNA delivery: effect of polymer and RNA structural parameters on polyplex assembly and gene knockdown

Loczenski Rose, Vanessa and Shubber, Saif and Sajeesh, S. and Spain, Sebastian G. and Puri, Sanyogitta and Allen, Stephanie and Lee, Dong-Ki and Winkler, G. Sebastiaan and Mantovani, Giuseppe (2015) Phosphonium polymethacrylates for siRNA delivery: effect of polymer and RNA structural parameters on polyplex assembly and gene knockdown. Biomacromolecules, 16 (11). pp. 3480-3490. ISSN 1525-7797

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Abstract

Synthetic polymers containing quaternary phosphonium salts are an emerging class of materials for the delivery of oligo/polynucleotides. In this work, cationic phosphonium salt-containing polymethacrylates –and their corresponding ammonium analogues– were synthesized by RAFT polymerization. Both the nature of the charged heteroatom (N vs. P) and the length of the spacer separating the cationic units along the polymer backbone (oxyethylene vs. trioxyethylene) were systematically varied. Polymers efficiently bound siRNA at N+/P- or P+/P- ratios of 2 and above. At a 20:1 ratio, small polyplexes (Rh: 4-15 nm) suitable for cellular uptake were formed that displayed low cytotoxicity. Whilst siRNA polyplexes from both ammonium and phosphonium polymers were efficiently internalised by GFP-expressing 3T3 cells, no knockdown of GFP expression was observed. However, 65% Survivin gene knockdown was observed when short interfering RNA (siRNA) was replaced with novel, multimerised long interfering liRNA (liRNA) in HeLa cells, demonstrating the importance of RNA macromolecular architecture on RNA-mediated gene silencing.

Item Type: Article
Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.biomac.5b00898
Schools/Departments: University of Nottingham UK Campus > Faculty of Science > School of Pharmacy
Identification Number: https://doi.org/10.1021/acs.biomac.5b00898
Depositing User: Mantovani, Giuseppe
Date Deposited: 18 Aug 2016 10:51
Last Modified: 23 Sep 2016 06:42
URI: http://eprints.nottingham.ac.uk/id/eprint/35894

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