Magnetization relaxation mechanisms strongly influence how magnetic nanoparticles respond to high-frequency fields in applications such as magnetic hyperthermia. The dominant mechanism depends on the mobility of the particles, which will be affected in turn by their microenvironment. In this study AC susceptometry was used to follow the in situ magnetic response of model systems of blocked and superparamagnetic nanoparticles, following their cellular internalization and subsequent release by freeze-thaw lysis. The AC susceptibility signal from internalized particles in live cells showed only Néel relaxation, consistent with measurements of immobilized nanoparticle suspensions. However, Brownian relaxation was restored after cell lysis, indicating that the immobilization effect was reversible and that nanoparticle integrity was maintained in the cells. The results presented demonstrate that cellular internalization can disable Brownian relaxation, which has significant implications for designing suitable nanoparticles for intracellular hyperthermia applications. Further to this, the results highlight the possibility that particles could be released in reusable form from degrading cells following hyperthermia treatment, and subsequently reabsorbed by viable cells.

The magnetic moment and anisotropy of magnetite nanoparticles can be optimised by doping with transition metal cations, enabling their properties to be tuned for different biomedical applications. In this study, we assessed the suitability of bacterially synthesized zinc- and cobalt-doped magnetite nanoparticles for biomedical applications. To do this we measured cellular viability and activity in primary human bone marrow-derived mesenchymal stem cells and human osteosarcoma-derived cells. Using AC susceptibility we studied doping induced changes in the magnetic response of the nanoparticles both as stable aqueous suspensions and when associated with cells. Our findings show that the magnetic response of the particles was altered after cellular interaction with a reduction in their mobility. In particular, the strongest AC susceptibility signal measured in vitro was from cells containing high-moment zinc-doped particles, whilst no signal was observed in cells containing the high-anisotropy cobalt-doped particles. For both particle types we found that the moderate dopant levels required for optimum magnetic properties did not alter their cytotoxicity or affect osteogenic differentiation of the stem cells. Thus, despite the known cytotoxicity of cobalt and zinc ions, these results suggest that iron oxide nanoparticles can be doped to sufficiently tailor their magnetic properties without compromising cellular biocompatibility.

opened the discussion of the paper by Peter Dobson: Is a size of below 20 nm critical to achieve cell penetration by nanoparticles? Peter Dobson responded: No, I chose this as a typical size. I believe that the most important point is the surface chemistry and that particle size could be a secondary factor. On the other hand, smaller particles of <20 nm will induce a distortion of the outer cell membrane enabling the particle to penetrate by endocytosis, but this requires a strong affinity brought about by the nanoparticlecell surface interaction. Ivan Parkin remarked: The antimicrobial properties of nanodiamond may have been misrepresented in the literature as the commercial solutions contain a variety of antimicrobial agents. Studies must make sure that these are not present if antimicrobial analyses are to be performed. Peter Dobson replied: I fully agree, but on the other hand nanodiamond has got unique energy levels with respect to water and related systems. 1

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