Efficient siRNA delivery to mammalian cells using layered double hydroxide nanoparticles.
Although siRNAs have surpassed expectations in experiments to alter gene expression in vitro, the lack of an efficient in vivo delivery system still remains a challenge in siRNA therapeutics development and has been recognized as a major hurdle for clinical applications. In this paper we describe an inorganic nanoparticle-based delivery system that is readily adaptable for in vivo systems. Layered double hydroxide (LDH) nanoparticles, a family of inorganic crystals, tightly bind, protect, and release siRNA molecules and deliver them efficiently to mammalian cells in vitro. The uptake of siRNA-loaded LDH nanoparticles occurs via endocytosis, whereby the nanoparticles dissolve due to the low pH in the endosome, thereby aiding endosomal escape into the cytoplasm. The influence of LDH nanoparticles on cell viability and proliferation is negligible at concentrations <or=0.050 mg mL(-1), and a pronounced down-regulation of protein expression upon LDH mediated siRNA transfection of HEK293T cells is observed.
Ladewig
Katharina
K
The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, St Lucia QLD 4072, Australia.
Niebert
Marcus
M
Xu
Zhi P
ZP
Gray
Peter P
PP
Lu
Gao Q M
GQ
D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006878:Hydroxides / Q000737:chemistry* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009841:Oligonucleotides / Q000378:metabolism; D010316:Particle Size; D034741:RNA, Small Interfering / Q000378:metabolism*; D014162:Transfection
D006878:Hydroxides; D009841:Oligonucleotides; D034741:RNA, Small Interfering; D016650:Fluorescein-5-isothiocyanate