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

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• 作者：E. Lellouche ; L. L. Israel ; M. Bechor ; S. Attal ; E. Kurlander ; V. A. Asher ; A. Dolitzky ; L. Shaham ; S. Izraeli ; J.-P. Lellouche ; S. Michaeli
• 刊名：Bioconjugate Chemistry
• 出版年：2015
• 出版时间：August 19, 2015
• 年：2015
• 卷：26
• 期：8
• 页码：1692-1701
• 全文大小：457K
• ISSN：1520-4812

文摘

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 (纬-Fe₂O₃) nanoparticles, termed magnetic reagent for efficient transfection (MagRET), which are composed of a maghemite core that is surface-doped by lanthanide Ce^3/4+ 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鈥?00% 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.