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

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

Author information

1
Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States.
2
Department of Bioengineering, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, United States.
3
Division of Diagnostic and Surgical Sciences, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States.
4
Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States; Department of Bioengineering, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, United States.
5
Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States; Department of Bioengineering, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, United States. Electronic address: leemin@ucla.edu.

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

PMID:
26302903
PMCID:
PMC4624027
DOI:
10.1016/j.jconrel.2015.08.031
[Indexed for MEDLINE]
Free PMC Article

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