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

Research output: Contribution to journalArticle

Abstract

RNA interference (RNAi) 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
LanguageEnglish
JournalJournal of Liposome Research
Publication statusAccepted/In press - 28 Sep 2018

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Surface-Active Agents
Small Interfering RNA
Luciferases
Proteins
Liposomes
Messenger RNA
Microfluidics
In Vitro Techniques
Regulator Genes
RNA Interference
Melanoma
Cell Membrane
Therapeutics
Genes

Keywords

  • nisomes
  • nanoparticles
  • microfluidics
  • RNA interference
  • drug delivery

Cite this

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title = "Proof of concept studies for siRNA delivery by non-ionic surfactant vesicles: in vitro and in vivo evaluation of protein knockdown",
abstract = "RNA interference (RNAi) 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 = "nisomes, nanoparticles, microfluidics, RNA interference, drug delivery",
author = "Obeid, {Mohammad A.} and Christine Duf{\`e}s and Sukrut Somani and Mullen, {Alexander B.} and Tate, {Rothwelle J.} and Ferro, {Valerie A.}",
year = "2018",
month = "9",
day = "28",
language = "English",
journal = "Journal of Liposome Research",
issn = "0898-2104",

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T1 - Proof of concept studies for siRNA delivery by non-ionic surfactant vesicles

T2 - Journal of Liposome Research

AU - Obeid, Mohammad A.

AU - Dufès, Christine

AU - Somani, Sukrut

AU - Mullen, Alexander B.

AU - Tate, Rothwelle J.

AU - Ferro, Valerie A.

PY - 2018/9/28

Y1 - 2018/9/28

N2 - RNA interference (RNAi) 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

AB - RNA interference (RNAi) 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

KW - nisomes

KW - nanoparticles

KW - microfluidics

KW - RNA interference

KW - drug delivery

UR - https://www.tandfonline.com/loi/ilpr20

M3 - Article

JO - Journal of Liposome Research

JF - Journal of Liposome Research

SN - 0898-2104

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