Proof of concept studies for siRNA delivery by nonionic surfactant vesicles: in vitro and in vivo evaluation of protein knockdown

J Liposome Res. 2019 Sep;29(3):229-238. doi: 10.1080/08982104.2018.1531424. Epub 2019 Jan 1.

Abstract

RNA interference is an effective and naturally occurring post-transcriptional gene regulatory mechanism. This mechanism involves the degradation of a target messenger RNA (mRNA) through the introduction of short interfering RNA (siRNA) that is complementary to the target mRNA. The application of siRNA-based therapeutics is limited by the development of an effective delivery system, as naked siRNA is unstable and cannot penetrate the cell membrane. In this study, we investigated the use of cationic niosomes (CN) prepared by microfluidic mixing for siRNA delivery. In an in vitro model, these vesicles were able to deliver anti-luciferase siRNA and effectively suppress luciferase expression in B16-F10 mouse melanoma cells. More importantly, in an in vivo mouse model, intratumoral administration of CN-carrying anti-luciferase siRNA led to significant suppression of luciferase expression compared with naked siRNA. Thus, we have established a novel and effective system for the delivery of siRNA both in vitro and in vivo, which shows high potential for future application of gene therapeutics.

Keywords: Niosomes; RNA interference; drug delivery; microfluidics; nanoparticles.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • Female
  • Gene Knockdown Techniques / methods*
  • Gene Silencing
  • Gene Transfer Techniques
  • Liposomes / chemistry*
  • Luciferases / genetics
  • Luciferases / metabolism
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanocapsules / chemistry*
  • Proof of Concept Study
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / metabolism
  • Surface-Active Agents / chemistry*

Substances

  • Liposomes
  • Nanocapsules
  • RNA, Small Interfering
  • Surface-Active Agents
  • Luciferases