Abstract
Magnetic nanoparticles are increasingly used in medical applications, including cancer treatment by magnetic hyperthermia. This protocol describes a solvothermal-based process to prepare, at the gram scale, ferrite nanoparticles with well-defined shape, i.e., nanocubes, nanostars and other faceted nanoparticles, and with fine control of structural/magnetic properties to achieve point-of-reference magnetic hyperthermia performance. This straightforward method comprises simple steps: (i) making a homogeneous alcoholic solution of a surfactant and an alkyl amine; (ii) adding an organometallic metal precursor together with an aldehyde molecule, which acts as the key shape directing agent; and (iii) reacting the mixture in an autoclave for solvothermal crystallization. The shape of the ferrite nanoparticles can be controlled by the structure of the aldehyde ligand. Benzaldehyde and its aromatic derivatives favor the formation of cubic ferrite nanoparticles while aliphatic aldehydes result in spherical nanoparticles. The replacement of the primary amine, used in the nanocubes synthesis, with a secondary/tertiary amine results in nanoparticles with star-like shape. The well-defined control in terms of shape, narrow size distribution (below 5%), compositional tuning and crystallinity guarantees the preparation, at the gram scale, of nanocubes/star-like nanoparticles that possess, under magnetic field conditions of clinical use, specific adsorption rates comparable to or even superior to those obtained through thermal decomposition methods, which are typically prepared at the milligram scale. Here, gram-scale nanoparticle products with benchmark features for magnetic hyperthermia applications can be prepared in ~10 h with an average level of expertise in chemistry.
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Data availability
Supporting data for this protocol can be found at https://doi.org/10.6084/m9.figshare.20155535.v1.
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Acknowledgements
This work was funded by EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC–Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))—ICARO no. 678109 (T.P.) and the AIRC Associazione per la Ricerca sul Cancro Foundation (AIRC IG-14527) (T.P.).
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H.G., G.M.R.R., N.S., B.T.M. and T.P. contributed intellectually and practically to the development of the technique.
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Key references using this protocol
Persano, S. et al. Pharmaceutics 13, 1668 (2021): https://doi.org/10.3390/pharmaceutics13101668
Pellegrino, T. et al. International patent WO 2020/222133 (2020): https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020222133
Pellegrino, T. et al. International patent WO 2022/090316 (2022): https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022090316
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Supplementary experimental section, water transfer protocols (Boxes 1–4), characterizations, Figs. 1–23, Tables 1–3 and References.
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Gavilán, H., Rizzo, G.M.R., Silvestri, N. et al. Scale-up approach for the preparation of magnetic ferrite nanocubes and other shapes with benchmark performance for magnetic hyperthermia applications. Nat Protoc 18, 783–809 (2023). https://doi.org/10.1038/s41596-022-00779-3
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DOI: https://doi.org/10.1038/s41596-022-00779-3
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