Ce3/4+ cation-functionalized maghemite nanoparticles towards siRNA-mediated gene silencing

Pre-formed Massart magnetite (Fe3O4) nanoparticles (NPs) have been successfully modified by positively charged lanthanide Ce(III/IV) cations/[CeLn](3/4+) complexes by using a strong mono-electronic Ceric Ammonium Nitrate oxidant (CAN) as a Ce donor. The doping process is promoted by high-power ultrasonic irradiation. The reaction has been statistically optimized by Design of Experiments (DoE, MINITAB (R) 16 DoE software) to afford globally optimized magnetically responsive ultra-small 6.61 + 2.04 nm-sized CAN(DOE)-gamma-Fe2O3 NPs that are highly positively charged (xi potential: +45.7 mV). This innovative inorganic DoE-optimized NP surface modification by [CeLn](3/4+) complexes enables an effective "fully inorganic-type" coordination attachment of a branched poly-cationic 25 kDa b-PEI25 polymer for siRNA loading and gene silencing. This innovative NP platform technology paves an efficient way for the successful development of a wide range of biomedicine and diagnostic-related applications.