Delivery of siRNA via cationic Sterosomes to enhance osteogenic differentiation of mesenchymal stem cells

J Control Release. 2015 Nov 10;217:42-52. doi: 10.1016/j.jconrel.2015.08.031. Epub 2015 Aug 21.

Abstract

Noggin is a specific antagonist of bone morphogenetic proteins (BMPs) that can prevent the interaction of BMPs with their receptors. RNA interfering molecules have been used to downregulate noggin expression and thereby stimulate BMP signaling and osteogenesis. Cationic liposomes are considered one of the most efficient non-viral systems for gene delivery. In the past decade, non-phospholipid liposomes (Sterosomes) formulated with single-chain amphiphiles and high content of sterols have been developed. In particular, Sterosomes composed of stearylamine (SA) and cholesterol (Chol) display distinct properties compared with traditional phospholipid liposomes, including increased positive surface charges and enhanced particle stability. Herein, we report SA/Chol Sterosome and small interfering RNA (siRNA) complexes that significantly enhanced cellular uptake and gene knockdown efficiencies in adipose derived mesenchymal stem cells with minimal cytotoxicity compared with commercially available lipofectamine 2000. Furthermore, we confirmed osteogenic efficacy of these Sterosomes loaded with noggin siRNA in in vitro two- and three-dimensional settings as well as in a mouse calvarial defect model. The delivery of siRNA via novel SA/Chol Sterosomes presents a powerful method for efficient gene knockdown. These distinct nanoparticles may present a promising alternative approach for gene delivery.

Keywords: Cholesterol; Mesenchymal stem cells; Osteogenic differentiation; Stearylamine; Sterosomes; siRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Amines / chemistry
  • Animals
  • Carrier Proteins / genetics*
  • Cell Differentiation
  • Chitosan / analogs & derivatives
  • Chitosan / chemistry
  • Cholesterol / chemistry
  • Gene Silencing
  • Gene Transfer Techniques*
  • Hydrogels / chemistry
  • Liposomes
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mice, Inbred C57BL
  • Mice, Nude
  • Nanoparticles / administration & dosage
  • Nanoparticles / toxicity
  • Osteogenesis*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry
  • Radiography
  • Skull / diagnostic imaging
  • Skull / injuries

Substances

  • Amines
  • Carrier Proteins
  • Hydrogels
  • Liposomes
  • RNA, Small Interfering
  • noggin protein
  • Chitosan
  • Cholesterol
  • stearylamine