Cationic solid lipid nanoparticles reconstituted from low density lipoprotein components for delivery of siRNA.
Cationic solid lipid nanoparticles (SLN), reconstituted from natural components of protein-free low-density lipoprotein, were used to deliver small interfering RNA (siRNA). The cationic SLN was prepared using a modified solvent-emulsification method. The composition was 45% (w/w) cholesteryl ester, 3% (w/w) triglyceride, 10% (w/w) cholesterol, 14% (w/w) dioleoylphosphatidylethanolamine (DOPE), and 28% (w/w) 3beta-[ N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol (DC-chol). The SLN had a mean diameter of 117+/-12 nm and a surface zeta potential value of +41.76+/-2.63 mV. A reducible conjugate of siRNA and polyethylene glycol (PEG) (siRNA-PEG) was anchored onto the surface of SLN via electrostatic interactions, resulting in stable complexes in buffer solution and in even 10% serum. Under an optimal weight ratio of DC-chol of SLN and siRNA-PEG conjugate, the complexes exhibited higher gene silencing efficiency of GFP and VEGF than that of polyethylenimine (PEI) 25K with showing much reduced cell cytotoxicity. Flow cytometry results also showed that siRNA-PEG/SLN complexes were efficiently taken up by cells. Surface-modified and reconstituted protein-free LDL mimicking SLN could be utilized as noncytotoxic, serum-stable, and highly effective carriers for delivery of siRNA.
Kim
Hyun Ryoung
HR
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Kim
In Kyoung
IK
Bae
Ki Hyun
KH
Lee
Soo Hyeon
SH
Lee
Yuhan
Y
Park
Tae Gwan
TG
D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics*
D002412:Cations; D017077:Culture Media, Conditioned; D008077:Lipoproteins, LDL; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D011094:Polyethyleneimine