Comparing Gene Silencing and Physiochemical Properties in siRNA Bound Cationic Star-Polymer Complexes

Megan Dearnley, Nicholas P Reynolds, Peter Cass, Xiaohu Wei, Shuning Shi, A. Aalam Mohammed, Tam Le, Pathiraja Gunatillake, Mark L Tizard, San H. Thang, Tracey M Hinton

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

The translation of siRNA into clinical therapies has been significantly delayed by issues surrounding the delivery of naked siRNA to target cells. Here we investigate siRNA delivery by cationic acrylic polymers developed by Reversible Addition-Fragmentation chain Transfer (RAFT) mediated free radical polymerization. We investigated cell uptake and gene silencing of a series of siRNA-star polymer complexes both in the presence and absence of a protein "corona". Using a multidisciplinary approach including quantitative nanoscale mechanical-atomic force microscopy, dynamic light scattering and nanoparticle tracking analysis we have characterized the nanoscale morphology, stiffness, and surface charge of the complexes with and without the protein corona. This is one of the first examples of a comprehensive physiochemical analysis of siRNA-polymer complexes being performed alongside in vitro biological assays, allowing us to describe a set of desirable physical features of cationic polymer complexes that promote gene silencing. Multifaceted studies such as this will improve our understanding of structure-function relationships in nanotherapeutics, facilitating the rational design of polymer-mediated siRNA delivery systems for novel treatment strategies.

Original languageEnglish
Pages (from-to)3532-3546
Number of pages15
JournalBiomacromolecules
Volume17
Issue number11
DOIs
Publication statusPublished - 14 Nov 2016
Externally publishedYes

Keywords

  • Polyethyleneimine
  • nonviral gene
  • Transfection

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