The influence of cation incorporation and leaching in the properties of Mn-doped nanoparticles for biomedical applications

[Hypothesis]: Superparamagnetic MnxFe3-xO4 nanoparticles are promising materials for applications in biomedicine and other fields. Small variations in the Mn/Fe ratio have a strong impact on the properties of the nanoparticles. Those variations may be caused by the synthesis itself and by common post-synthesis manipulations like surface modification.[Experiments]: Mn-ferrite nanoparticles have been prepared changing systematically the Mn/Fe ratio of the metal precursors and repeating each reaction three times. Nanoparticles were subjected to surface modification with two different and typical molecules to stabilize them in aqueous media. The discrepancy in the Mn/Fe ratios of the precursors with the ones measured after the synthesis and the surface modification have been studied, as well as its impact on the saturation magnetization, blocking temperature, contrast enhancement for magnetic resonance imaging, magnetic heating, and on the cytotoxicity.[Findings]: Mn is incorporated in the nanoparticles in a relatively lower amount than Fe and, as this report shows for the first time, both Mn and Fe ions leach out from the nanoparticles during the surface modification step. The blocking temperature decreases exponentially as the Mn/Fe ratio increases. The transverse and longitudinal relaxation times and the magnetic heating ability change appreciably even with small variations in the composition.This work was supported by the Spanish Ministry of Economy and Competitiveness (project MAT2015-71806-R, SAF2017-87305-R, PGC2018-096016-B-I00), Comunidad de Madrid (projects P2018/NMT-4321, NANOMAGCOST-CM, and B2017/BMD-3867, RENIM-CM), and European Commission H2020 programme (project NOCANTHER, grant agreement no. 685795). IMDEA Nanociencia acknowledges support from the 'Severo Ochoa' Programme for Centres of Excellence in R&D (grant SEV-2016-0686). DG-S gratefully acknowledges Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid y del Fondo Social Europeo (PEJD-2016/IND-2293 fellowship), PMR acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686), NLG thanks the Spanish Education Ministry for the funding (FPU18/02323) and Ayuntamiento de Madrid for the grant to live at Residencia de Estudiantes del CSIC. L.G. acknowledges financial support from the Ramón y Cajal program (RYC-2014-15512).Peer reviewe