Journal
BIOCONJUGATE CHEMISTRY
Volume 26, Issue 8, Pages 1692-1701Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.5b00276
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Funding
- Israeli National Nanotechnology Initiative in the Focal Technology Area: Nanomedicines for Personalized Theranostics
- I-core grant from the Israel Science Foundation [40/11]
- VIIth Framework RTD European Project (FP7-NMP-2010-LARGE-4 area) - Large Collaborative Project SaveMe [263307]
- Israel Ministry of Industry Trade
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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 (gamma-Fe2O3) nanoparticles, termed magnetic reagent 0 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 [CeLn](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.
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