Ce^3/4+ 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/[CeL_n]^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® 16 DoE software) to afford globally optimized magnetically responsive ultra-small 6.61 ± 2.04 nm-sized CAN_DOE-γ-Fe₂O₃ NPs that are highly positively charged (ξ potential: +45.7 mV). This innovative inorganic DoE-optimized NP surface modification by [CeL_n]^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.