Modifying internal organization and surface morphology of siRNA lipoplexes by sodium alginate addition for efficient siRNA delivery

J Colloid Interface Sci. 2019 Mar 22;540:342-353. doi: 10.1016/j.jcis.2019.01.043. Epub 2019 Jan 14.

Abstract

Vectorized small interfering RNAs (siRNAs) are widely used to induce specific mRNA degradation in the intracellular compartment of eukaryotic cells. Recently, we developed efficient cationic lipid-based siRNA vectors (siRNA lipoplexes or siLex) containing sodium alginate (Nalg-siLex) with superior efficiency and stability properties than siLex. In this study, we assessed the physicochemical and some biological properties of Nalg-siLex compared to siLex. While no significant differences in size, ζ potential and siRNA compaction were detected, the addition of sodium alginate modified the particle morphology, producing smoother and heterogeneous particles characterized by transmission electron microscopy. We also noted that Nalg-siLex have surface differences observed by X-ray photoelectron spectroscopy. These differences could arise from an internal reorganization of components induced by the addition of sodium alginate, that is indicated by Small-Angle X-ray Scattering results. Moreover, Nalg-siLex did not trigger significant hepatotoxicity nor inflammatory cytokine secretion compared to siLex. Taken together these results suggest that sodium alginate played a key role by structuring and reinforcing siRNA lipoplexes, leading to more stable and efficient delivery vector.

Keywords: Anionic polymer; Cationic lipid; Delivery system; Nanoparticle; RNA interference; Structure.

MeSH terms

  • Alginates / chemistry*
  • Animals
  • Cations / chemistry
  • Cell Line
  • Female
  • Gene Transfer Techniques*
  • Lipids / chemistry
  • Liposomes / chemistry*
  • Mice, Inbred C57BL
  • Particle Size
  • RNA Interference*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics
  • Static Electricity

Substances

  • Alginates
  • Cations
  • Lipids
  • Liposomes
  • RNA, Small Interfering