OPTIMAL VERSATILE SURFACE ENGINEERING OF LANTHANIDE CATION-DOPED γ-MAGHEMITE NANOPARTICLES: SIRNA-MEDIATED GENE SILENCING IN THE CASE OF OVARIAN CANCER

Jean-Paul Lellouche 1 Yifat Harel-Ashkenazy 1 Stella Ostrovsky 1 Ziv Porat 2 Shulamit Michaeli 2
1Department of Chemistry, Nanomaterials Research Center (BINA), Bar-Ilan University, Ramat-Gan, Israel
2Faculty of Life Sciences, Nanomaterials Research Center (BINA), Bar-Ilan University, Ramat-Gan, Israel

Iron oxide (FexOy) nanoparticles (NPs) are currently widely used in numerous biotechnology applications (magnetism-driven cell separation/cell tracking, magnetic field-guided drug/gene delivery, non-invasive tissue MRI, anti-cancer hyperthermia). But serious drawbacks like challenging detrimental NPs aggregation and controlled NPs surface functionalization versatility request quite innovative solutions.

Our recent R&D work in this field led to the discovery of a novel method/concept for promoting (i) the effective anti-aggregation control of 5.0-6.5 nm-sized hydrophilic super-paramagnetic maghemite (γ-Fe2O3) NPs, and (ii) its successful use for NPs functionalization/versatile NPs surface engineering toward siRNA-mediated gene delivery/silencing cancer therapy-relevant applications. Such an innovative NPs surface engineering methodology exploits a controlled Design Of Experiment globally optimized high-power ultrasound (US)-assisted lanthanide metal Ce(III/IV) cation/complex doping of the NPs surface towards 45/50 nm-sized (DLS) maghemite NPs. This US-nanofabrication led to highly positive hydrophilic NPs (+41.0-+50.0 mV ζ-potential range). Such a powerful Ce3/4+ cation/complex-doping process enabled (i) an effective charge control of potential NPs aggregation, (ii) the full NPs water compatibility for biological applications, and finally (iii) the effective development of quite versatile surface engineering chemistries using its Ce3/4+ cation/complex-based coordination chemistry involving any Lewis basis biomolecule/organic species (hyaluronic/alginic acids, 25 kDa polyethyleneimine, etc.…), - covalent binding enabling 2nd step chemical derivatizations (NPs cancer cell targeting).

Such a versatile NPs surface engineering enabled the discovery of specifically chemically modified γ-Fe2O3 NPs that disclosed powerful anti-ovarian cancer cell activity (tumor progression stopping) via specific effective PLK-1 siRNA delivery.1

  1. J.-P. Lellouche et al., Magnetic Inorganic Iron-Based Nanoparticles - Generalities and Use in Drug Delivery, Patent Application, 2014, PCT/IL2014/050064








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