title: Reduction in the size of layered double hydroxide nanoparticles enhances the efficiency of siRNA delivery.
abstract: Small interfering RNAs (siRNAs) are a potentially powerful new class of pharmaceutical drugs for many disease. However, the delivery of unprotected siRNAs is ineffective due to their susceptibility to degradation by ubiquitous nucleases under physiological conditions. Layered double hydroxide nanoparticles (LDHs) have been found to be efficient carriers of anionic drugs and nucleic acids. Our previous research has shown that LDHs (with the Z-average particle size of approximately 110 nm) can mediate siRNA delivery in mammalian cells, resulting in gene silencing. However, short double-stranded nucleic acids are mostly adsorbed onto the external surface and not well protected by LDHs. In order to enhance the intercalation of siRNA into the LDH interlayer and the efficiency of subsequent siRNA delivery, we prepared smaller LDHs (with the Z-average particle size of approximately 45 nm) with an engineered non-aqueous method. We demonstrate here that dsDNA/siRNA is more effectively intercalated into these small LDH nanoparticles, more dsDNA/siRNA is transfected into HEK 293T cells, and more efficient silencing of the target gene is achieved using smaller LDHs. Thus, smaller LDH particles have greater potential as a delivery system for the application of RNA interference.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Queensland 4072, Australia.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Helen M
authors.initials: HM
authors.lastname: Cooper
authors.forename: Ji Zhi
authors.initials: JZ
authors.lastname: Zhou
authors.forename: Perry F
authors.initials: PF
authors.lastname: Bartlett
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Xu
mesh_terms: D004247:DNA / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection / Q000379:methods*
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering; D004247:DNA