Article

Drug Delivery and Translational Research

, Volume 1, Issue 1, pp 25-33

First online:

Phospholipid–polyethylenimine conjugate-based micelle-like nanoparticles for siRNA delivery

  • Gemma NavarroAffiliated withCenter for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University
  • , Rupa R. SawantAffiliated withCenter for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University
  • , Sean EssexAffiliated withCenter for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University
  • , Conchita Tros de ILarduyaAffiliated withDepartment of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra
  • , Vladimir P. TorchilinAffiliated withCenter for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University Email author 

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Abstract

Gene silencing using small interfering RNA (siRNA) is a promising therapeutic strategy for the treatment of various diseases, in particular, cancer. Recently, our group reported on a novel gene carrier, the micelle-like nanoparticle (MNP), based on the combination of a covalent conjugate of phospholipid and polyethylenimine (PLPEI) with polyethylene glycol (PEG) and lipids. These long-circulating MNPs loaded with plasmid DNA-mediated gene expression in distal tumors after systemic administration in vivo. In the current study, we investigated the potential of MNPs for siRNA delivery. MNPs were prepared by condensing siRNA with PLPEI at a nitrogen/phosphate ratio of 10, where the binding of siRNA is complete. The addition of a PEG/lipid coating to the PLPEI complexes generated particles with sizes of ca. 200 nm and a neutral surface charge compared with positively charged PLPEI polyplexes without the additional coating. MNPs protected the loaded siRNA against enzymatic digestion and enhanced the cellular uptake of the siRNA payload. MNPs carrying green fluorescent protein (GFP)-targeted siRNA effectively downregulated the gene in cells that stably express GFP. Finally, MNPs were non-toxic at a wide range of concentrations and for different cell lines.

Keywords

Nanoparticle Gene delivery siRNA delivery Polyethylenimine (PEI) Polyethylene glycol (PEG) Self-assembly Lipid/PEG coating