Design of Anti-Fouling and No-Cytotoxic Magnetic Nanoparticles for siRNA Delivery to Neuroblastoma Cells

  • Dr Cyrille Boyer, CAMD, UNSW, Australia, Australia
  • Prof Thomas Davis, CAMD, UNSW, Australia, Australia
  • Prof Maria Kavalaris, Childreen Institut, UNSW, Australia, Australia
  • Dr Joshua McCarol, Childreen Institut, UNSW, Australia, Australia
  • Prof Rose Amal, UNSW, Australia
  • Dr Wey Yang Teoh, UNSW, Australia

Iron oxide nanoparticles (IONPs) are one of the major classes of nanomaterials (with gold nanoparticles) able to revolutionize current clinical diagnostic and therapeutic techniques. Indeed, their unique physical-properties, i.e. high surface area onto volume ratio, and their supermagnetism properties confers original and useful properties for medical applications as magnetic resonance imagery, drug and gene deliveries and bio-separation. In this presentation, a new strategy is reported for the synthesis and the functionalization of ONPs, with a diameter of 8 nm. These nanoparticles have been coated with two different polymers synthesized via RAFT polymerization, i.e. poly(oligoethylene glycol) methyl ether acrylate (P(OEG-A) and poly(dimethylaminoethyl acrylate) (P(DMAEA)). The polymers were attached to the nanoparticle surface using two different strategies, with the aim of creating an internal layer of P(DMAEA) and an outer shell of P(OEG-A). The first approach applied a grafting “onto” of phosphonic terminated diblock P(DMAEA-b-OEG-A) polymers with the attachment occurring at the P(DMAEA) terminus. The second approach involved the simultaneous self-assembly of the two individual homopolymers.
The internal cationic layer, P(DMAEMA), was exploited for the complexation of siRNA, thereby generating IONP siRNA nano-carriers with anti-fouling P(OEG-A) shells. The transfection efficiency was assessed using human neuroblastoma cells both in the presence and absence of a magnetic field. The transfection efficiency was found to be comparable to a commercial transfection agent, i.e. lipofectamine in the presence of a magnetic field, determined by both fluorescence microscopy and flow cytometry. Cytotoxicity studies revealed that the IONP carriers were non-toxic to Neuroblastoma and 3t3 cells.