Amine-functionalized gold nanoparticles as non-cytotoxic and efficient intracellular siRNA delivery carriers.
Gold nanoparticles chemically modified with primary amine groups were developed as intracellular delivery vehicles for therapeutic small interfering RNA (siRNA). The positively charged gold nanoparticles could form stable polyelectrolyte complexes through electrostatic interactions with negatively charged siRNA-polyethylene glycol (PEG) conjugates having a cleavable di-sulfide linkage under reductive cytosol condition. The resultant core/shell type polyelectrolyte complexes surrounded by a protective PEG shell layer had a well-dispersed nanostructure with a hydrodynamic diameter of 96.3+/-25.9 nm, as determined by dynamic light scattering and transmission electron microscopy. Confocal laser scanning microscopy revealed that the nanosized polyelectrolyte complexes were efficiently internalized in human prostate carcinoma cells, and thus enhanced intracellular uptake of siRNA. Furthermore, the siRNA/gold complexes significantly inhibited the expression of a target gene within the cells without showing severe cytotoxicity. The current study demonstrated that positively charged gold nanoparticles could be potentially applied for intracellular delivery of siRNA.
Lee
Soo Hyeon
SH
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Bae
Ki Hyun
KH
Kim
Sun Hwa
SH
Lee
Kyu Ri
KR
Park
Tae Gwan
TG
D000588:Amines / Q000737:chemistry*; D016503:Drug Delivery Systems; D004573:Electrolytes / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000737:chemistry; D008027:Light; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
D000588:Amines; D004573:Electrolytes; D011108:Polymers; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D006046:Gold