• Endocytotic potential governs magnetic particle loading in dividing neural cells: studying modes of particle inheritance

      Tickle, Jacqueline A.; Jenkins, Stuart I.; Polyak, Boris; Pickard, Mark R.; Chari, Divya M.; Keele University, United Kingdom; Drexel University College of Medicine, Philadelphia, USA (Future Medicine, 2016-01-10)
      AIM: To achieve high and sustained magnetic particle loading in a proliferative and endocytotically active neural transplant population (astrocytes) through tailored magnetite content in polymeric iron oxide particles. MATERIALS & METHODS: MPs of varying magnetite content were applied to primary-derived rat cortical astrocytes ± static/oscillating magnetic fields to assess labeling efficiency and safety. RESULTS: Higher magnetite content particles display high but safe accumulation in astrocytes, with longer-term label retention versus lower/no magnetite content particles. Magnetic fields enhanced loading extent. Dynamic live cell imaging of dividing labeled astrocytes demonstrated that particle distribution into daughter cells is predominantly 'asymmetric'. CONCLUSION: These findings could inform protocols to achieve efficient MP loading into neural transplant cells, with significant implications for post-transplantation tracking/localization.
    • Influence of Amplitude of Oscillating Magnetic Fields on Magnetic Nanoparticle-Mediated Gene Transfer to Astrocytes

      Tickle, Jacqueline A.; Jenkins, Stuart I.; Pickard, Mark R.; Chari, Divya M.; Keele University, United Kingdom (World Scientific, 2014-08-07)
      Functionalized magnetic nanoparticles (MNPs) are emerging as a major nanoplatform for regenerative neurology, particularly as transfection agents for gene delivery. Magnetic assistive technology, particularly the recent innovation of applied oscillating magnetic fields, can significantly enhance MNP-mediated gene transfer to neural cells. While transfection efficiency varies with oscillation frequency in various neural cell types, the influence of oscillation amplitude has not yet been investigated. We have addressed this issue using cortical astrocytes that were transfected using MNPs functionalized with plasmid encoding a reporter protein. Cells were exposed to a range of oscillation amplitudes (100–1000 μm), using a fixed oscillation frequency of 1 Hz. No significant differences were found in the proportions of transfected cells at the amplitudes tested, but GFP-related optical density measurements (indicative of reporter protein expression) were significantly enhanced at 200 μm. Safety data show no amplitude-dependent toxicity. Our data suggest that the amplitude of oscillating magnetic fields influences MNP-mediated transfection, and a tailored combination of amplitude and frequency may further enhance transgene expression. Systematic testing of these parameters in different neural subtypes will enable the development of a database of neuro-magnetofection protocols — an area of nanotechnology research where little information currently exists.