Lipid‐Like Nanoparticles for Small Interfering RNA Delivery to Endothelial Cells

Abstract

Here we develop nanoparticles composed of lipid-like materials (lipidoids) to facilitate non-viral delivery of small interfering RNA (siRNA) to endothelial cells (ECs). Nanoparticles composed of siRNA and lipidoids with small size (~200 nm) and positive charge (~34 mV) were formed by self assembly of lipidoids and siRNA. Ten lipidoids were synthesized and screened for their ability to facilitate the delivery of siRNA into ECs. Particles composed of leading lipidoids show significantly better delivery to ECs than a leading commercially-available transfection reagent, Lipofectamine 2000. As a model of potential therapeutic application, nanoparticles composed of the top performing lipidoid, NA114, were studied for their ability to deliver siRNA targeting anti-angiogenic factor (SHP-1) to human ECs. Silencing of SHP-1 expression significantly enhanced EC proliferation and decreased EC apoptosis under a simulated ischemic condition.

Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-κB decoy oligodeoxynucleotide: A preliminary report

“…Lipofectamine 2000 was purchased from Invitrogen (Life Technologies, Pleasanton, CA). Lipidoid was generated as previously described [17]. The transfection protocols for Lipofectamine 2000 and Lipoid were followed according to the instructional manual.…”

Non-viral Delivery of Inductive and Suppressive Genes to Adipose-Derived Stem Cells for Osteogenic Differentiation

“…To overcome this hurdle, combinatorial polymer synthesis and high-throughput screening have been employed to facilitate the development of novel non-viral gene delivery systems (12,17,24). Biodegradable nanoparticulate PBAEs and synthetic lipid-like molecules ("lipidoids") are attractive options for non-viral gene delivery of DNA or siRNA to stem cells due to their high transfection efficiency and low toxicity (16,18). Our results demonstrate a dosedependent up-regulation of the osteoinductive gene, BMP2, at the mRNA level.…”

“…Lipidoid NA114 (Fig. 1a) was synthesized and used for siRNA complexation as previously described (18). Briefly, cells in each well of a 96-well plate were transfected with either 50 ng GNAS siRNA, 50 ng Noggin siRNA, or a combination of GNAS/ Noggin siRNAs (50 ng of each) complexed with the NA114 lipidoid at lipidoid/siRNA weight ratios of 5:1.…”

“…DNA transfection was performed using optimized poly(β-amino esters) (PBAE), a hydrolytically biodegradable polymer that can condense DNA to form nanoparticles (16). siRNA delivery was accomplished using lipid-like molecules as previously reported (17,18). To evaluate the effects of timing and duration of gene delivery on ADSC osteogenic differentiation, three groups received dual treatment of siNoggin and BMP2 DNA delivery at a later time point.…”

Multifunctional combinatorial-designed nanoparticles for nucleic acid therapy

“…The cationic poly(-amino ester) library of over 5,000 different constituents was then screened for use in non-viral gene therapy using plasmid DNA and siRNA delivery. Selection of "hits" from the poly(-amino ester) library allowed for further modification of the backbone structure to include lipid functionality and formulation of lipidoid-based nano-vesicles for siRNA encapsulation (10,(19)(20)(21).…”