TY - JOUR
T1 - MagRET Nanoparticles
T2 - An Iron Oxide Nanocomposite Platform for Gene Silencing from MicroRNAs to Long Noncoding RNAs
AU - Lellouche, E.
AU - Israel, L. L.
AU - Bechor, M.
AU - Attal, S.
AU - Kurlander, E.
AU - Asher, V. A.
AU - Dolitzky, A.
AU - Shaham, L.
AU - Izraeli, S.
AU - Lellouche, J. P.
AU - Michaeli, S.
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/8/19
Y1 - 2015/8/19
N2 - 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 [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.
AB - 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 [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.
UR - http://www.scopus.com/inward/record.url?scp=84939813706&partnerID=8YFLogxK
U2 - 10.1021/acs.bioconjchem.5b00276
DO - 10.1021/acs.bioconjchem.5b00276
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C2 - 26056709
AN - SCOPUS:84939813706
SN - 1043-1802
VL - 26
SP - 1692
EP - 1701
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 8
ER -
