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.

Mussel Adhesion‐Inspired Reverse Transfection Platform Enhances Osteogenic Differentiation and Bone Formation of Human Adipose‐Derived Stem Cells

“…The roughness of the pDA‐coated PLGA surface with serial loading of siRNA and LNP was about 20 nm (Figure b,c), which may not indicate particulate formation because amine groups of siRNA are consumed for binding to the pDA layer prior to LNP loading and thus cannot be provided for complexation with LNP. In contrast, the sLNP complexes loaded on the pDA‐coated PLGA surface increased the surface roughness up to ≈60 nm (Figure b,c), indicating particulate formation because it has been known that the sLNP complexes prepared by self‐assembly of siRNA and LNP form nanoparticles with a size of 50–200 nm …”

Combinatorial Synthesis of a Lipidoid Library by Thiolactone Chemistry: In Vitro Screening and In Vivo Validation for siRNA Delivery

“…DOPE is traditionally used during liposome formulation to increase the liposomal stability, aid fusion with cellular membranes, and boost endosomal escape of nucleic acid within cells. ,, However, the use of DOPE or any other helper lipid might make the formulation process more complicated and expensive; therefore, DOPE-free liposome formulations are implicated as interesting alternatives. Surprisingly, liposomes formulated from all three of the top-performing lipidoids without DOPE showed good stability and enhanced GFP-knockdown efficiency compared with the formulations prepared with DOPE (lipidoid:DOPE = 2:1) (Figure D).…”

Path-programmable water droplet manipulations on an adhesion controlled superhydrophobic surface

“…Lipidoid has been identified as a highly effective siRNA delivery vector with a higher transfection efficiency and lower cytotoxicity than currently available transfection reagents 36 . Lipidoid can mediate siRNA transfer into various types of cells and tissues, and thus it has shown great potential for therapeutic applications in diverse diseases 44 45 46 47 48 .…”