Phosphonium Polymethacrylates for Short Interfering RNA Delivery: Effect of Polymer and RNA Structural Parameters on Polyplex Assembly and Gene Knockdown
| Autor: | Dong Ki Lee, Sanyogitta Puri, G. Sebastiaan Winkler, Stephanie Allen, Saif Shubber, Giuseppe Mantovani, S. Sajeesh, Vanessa Loczenski Rose, Sebastian G. Spain |
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| Rok vydání: | 2015 |
| Předmět: |
Small interfering RNA
Polymers and Plastics Cell Survival Macromolecular Substances Green Fluorescent Proteins Bioengineering Polymerization Biomaterials chemistry.chemical_compound Mice Polymethacrylic Acids Cations Materials Chemistry Gene Knockdown Techniques Organic chemistry Animals Humans Phosphonium Gene Silencing Particle Size RNA Small Interfering Gene knockdown Chemistry Cationic polymerization RNA Chain transfer 3T3 Cells Gene Expression Regulation Polynucleotide Biophysics RNA Interference HeLa Cells |
| Zdroj: | Biomacromolecules. 16(11) |
| ISSN: | 1526-4602 |
| Popis: | 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 reversible addition-fragmentation chain transfer 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 short interfering RNA (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. While siRNA polyplexes from both ammonium and phosphonium polymers were efficiently internalized by green fluorescent protein (GFP)-expressing 3T3 cells, no knockdown of GFP expression was observed. However, 65% Survivin gene knockdown was observed when siRNA was replaced with novel, multimerized long interfering RNA in HeLa cells, demonstrating the importance of RNA macromolecular architecture on RNA-mediated gene silencing. |
| Databáze: | OpenAIRE |
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