MagRET Nanoparticles: An Iron Oxide Nanocomposite Platform for Gene Silencing from MicroRNAs to Long Noncoding RNAs

Silencing of RNA to knock down genes is currently one of the top priorities in gene therapies for cancer. However, to become practical the obstacle of RNA delivery needs to be solved. In this study, we used innovative maghemite (γ-Fe2O3) nanoparticles, termed magnetic reagent for efficient transfect...

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Bibliographic Details
Published in:Bioconjugate chemistry 2015-08, Vol.26 (8), p.1692-1701
Main Authors: Lellouche, E, Israel, L. L, Bechor, M, Attal, S, Kurlander, E, Asher, V. A, Dolitzky, A, Shaham, L, Izraeli, S, Lellouche, J.-P, Michaeli, S
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cell Cycle
Cell Proliferation
Drug Carriers
Ferric Compounds - chemistry
Gene Silencing
Gene therapy
Humans
Leukemia
Magnetite Nanoparticles - chemistry
Mice
Mice, Inbred BALB C
MicroRNAs - genetics
Nanocomposites
Nanocomposites - chemistry
Nanoparticles
Neoplasms - genetics
Neoplasms - pathology
Neoplasms - therapy
Oxidation
Polyethyleneimine - chemistry
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
RNA
RNA, Long Noncoding - genetics
RNA, Messenger - genetics
RNA, Small Interfering - genetics
Transfection
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
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Summary:Silencing of RNA to knock down genes is currently one of the top priorities in gene therapies for cancer. However, to become practical the obstacle of RNA delivery needs to be solved. In this study, we used innovative maghemite (γ-Fe2O3) nanoparticles, termed magnetic reagent for efficient transfection (MagRET), which are composed of a maghemite core that is surface-doped by lanthanide Ce3/4+ cations using sonochemistry. Thereafter, a polycationic polyethylenimine (PEI) polymer phase is bound to the maghemite core via coordinative chemistry enabled by the [CeL n ]3/4+cations/complex. PEI oxidation was used to mitigate the in vivo toxicity. Using this approach, silencing of 80–100% was observed for mRNAs, microRNAs, and lncRNA in a variety of cancer cells. MagRET NPs are advantageous in hard to transfect leukemias. This versatile nanoscale carrier can silence all known types of RNAs and these MagRET NPs with oxidized PEI are not lethal upon injection, thus holding promise for therapeutic applications, as a theranostic tool.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.5b00276