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

• Published in: Bioconjugate chemistry Vol. 26; no. 8; pp. 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: Journal Article
• Language: English
• Published: United States American Chemical Society 19.08.2015
• 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
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.5b00276

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.