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Bioconjug Chem. 2015 May 20;26(5):880-9. doi: 10.1021/acs.bioconjchem.5b00100. Epub 2015 Apr 8.

Unique Surface Modification of Silica Nanoparticles with Polyethylenimine (PEI) for siRNA Delivery Using Cerium Cation Coordination Chemistry.

Author information

1
†Department of Chemistry, Faculty of Exact Sciences, ‡The Mina and Everard Goodman Faculty of Life Sciences, and §Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002 Israel.

Abstract

The discovery of RNA interference (RNAi) as a naturally occurring mechanism for gene knockdown has attracted considerable attention toward the use of small interfering RNAs (siRNAs) for therapeutic purposes. The main obstacles of harnessing siRNAs as drugs are their inefficient delivery to cells and off-target effect making clinical applications very challenging. The positively charged, branched 25 kDa polyethylenimine (b-PEI) polymer is widely regarded as one of the most efficient nonviral commercially available transfection agents. However, it has also been shown that 25 kDa b-PEI is highly cytotoxic and can readily lead to cell death. In this specific context, this study presents the preparation and characterization of innovative 25 kDa b-PEI-decorated polycationic silica nanoparticles (SiO2 NPs) for cellular siRNA delivery and subsequent gene silencing. A new method of b-PEI attachment onto the SiO2 NP surface has been developed that makes use of cerium(III) cations (Ce(3+)), a lanthanide group element, as an effective noncovalent inorganic linker between both polyNH2-SiO2 nanoparticle (SPA NPs) surface and polycationic 25 kDa b-PEI polymer. Two resulting novel SPA-Ce-PEI NPs consist of similar amounts of b-PEI, while possessing different amounts of Ce(3+). Various analytical techniques (TEM, DLS, ζ potential, ICP-AES, and TGA) have been used to deeply characterize NPs physicochemical qualities. The observed results of Ce(3+)-dependent gene silencing and cytotoxic activities led us to conclusions about the role of Ce(3+)-N bonding during the chemical attachment of the 25 kDa b-PEI shell onto the NP surface.

PMID:
25830668
DOI:
10.1021/acs.bioconjchem.5b00100
[Indexed for MEDLINE]

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