Ex situ and in situ functionalized Yb/Fe nanoparticles obtained by scanning pulsed laser ablation in liquids: A route to obtain biofunctionalized multiplatform contrast agents for MRI and CT imaging

Two distinct strategies were used to improve the colloidal properties of hybrid Yb/Fe oxide NPs previously prepared by the pulsed liquid laser ablation process for use as a contrast agent in medical imaging. First, an exhaustive optimization process of the laser ablation synthesis parameters was carried out to reduce the hydrodynamic diameters of the Yb/Fe NPs. The hydrodynamic size was successfully reduced to <200 nm, thereby decreasing the polydispertivity index. Second, ex situ and in situ functionalization processes using glutathione, cysteamine, or polyethylenimine as capping agents have been developed to increase their colloidal stability at physiological pH values. Transmission electron microscopy, dynamic light scattering, Z-potential measurements, and Fourier Transform Infrared spectroscopy were used to examine the structure, morphology, colloidal and surface properties of Yb/Fe NPs. Colloidal stability of the Yb/Fe NPs as well as the linkage mechanism of functionalization have been studied extensively. This last parameter provides a critical information for subsequently bioconjugations in biomedical applications. Additionally, the biocompatibility of the Yb/Fe NPs was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) experiments. These results indicate more appropriate colloidal characteristics and higher biocompatibility for ex situ-functionalized Yb/Fe NPs, especially when the capping agent is glutathione. Additionally, these Yb/Fe NPs show good magnetic resonance imaging and X-ray computerized tomography imaging abilities, thereby indicating promising potential as dual contrast agents.This research has been funded by the Spanish Ministry of Economy and Competitiveness (MINECO) and FEDER [research projects MAT2015-67354R], the H2020 Action H2020-MSCA-IF-2014_ST [grant 656908-NIMBLIS] of the Executive Agency for Research Manages of EU Commission, the Proyectos Integradores MdM-IMEYMAT 2020 call (research project ULST-NANO), and the projects PECART-0096-2020 (Consejería Salud y Familias. JA Spain) and P20_01293 (Consejería Economía, Conocimiento, Empresas y Universidad. JA Spain). In addition, we acknowledge the received technical assistance from the SC-ICYT of the University of Cádiz. We also acknowledge to the Networking Research Centre on Bioengineering, Biomaterials, and Nanomedicine (CIBERBBN) (which is financed by the Instituto de Salud Carlos III (ISCIII) with assistance from the European Regional Development Fund (ERDF)) and the ICTS “NANBIOSIS”, specifically the FVPR/U20 (http://www.nanbiosis.es/portfolio/u20-in-vivo-experimentalplatform/) for providing access to the micro-CT. M.L. was supported by a post-doctoral grant of the Consejo Nacional de Ciencia y Tecnología from Mexico (CONACYT, no 619639).Peer reviewe

Scanning pulsed laser ablation in liquids: An alternative route to obtaining biocompatible YbFe nanoparticles as multiplatform contrast agents for combined MRI and CT imaging

Ytterbium ferrites are being used in many promising applications, such as visible-light photocatalysis, solar cells, magnetooptic devices, electro-magnetic equipment, etc., due to their fantastic ferroelectric and ferromagnetic properties. However, despite their good magnetic and radiopaque features, the use of ytterbium ferrites as multiplatform contrast agents in magnetic resonance imaging (MRI) and X-ray computed tomography (CT) is still under-developed. This is mainly due to difficulties in obtaining stable and biocompatible aqueous colloidal dispersions of ytterbium ferrite nanoparticles. In order to overcome this limitation, this work explores an eco-friendly method to directly synthesize such dispersions by liquid-assisted pulsed laser ablation of ytterbium ferrite massive targets. First, orthorhombic bulk YbFeO3 targets were obtained by a reaction-sintering method. Then, colloidal dispersions of nanoparticles were produced directly in both distilled water and ethanol by irradiating the bulk YbFeO3 targets with high-power infrared nanosecond lasers pulses. A battery of techniques has been used to characterize the as synthesized YbFeO3 targets and colloidal dispersions of YbFe nanoparticles to determine their composition, structure, magnetic properties, X-ray attenuation potentials, and colloidal properties. Moreover, the biocompatibility of the systems was also analysed by MTT cell viability assay. Results indicated that the use of distilled water as ablation medium yields colloidal dispersions consisted mainly of paramagnetic ytterbium ferrite nanoparticles. Contrarily, the use of ethanol as solvent leads to colloidal dispersions of polycrystalline nanoparticles with both ferromagnetic and paramagnetic behaviour, due to the coexistence, in each nanoparticle, of ytterbium ferrite, ytterbium oxide, and iron oxide crystalline phases. Both colloidal dispersions exhibit also high biocompatibility and suitable X-ray attenuation properties. Moreover, they show bio-safe hydrodynamic sizes (lower than 200 nm) with acceptable overall hydrodynamic polydispersity index values (under 0.4), being stable in water for several weeks. These results pave the way for the future evaluation of Yb–Fe based nanoparticles as multiplatform contrast agents in multimodal MRI and CT imaging.This research has been funded by the Spanish Ministry of Economy and Competitiveness (MINECO) and FEDERthrough the research project MAT2015-67354R, and a MSCA-IF postdoctoral fellowship from the Marie Curie action 2014 [grant 656908-NIMBLIS] of the H2020 program of the Executive Agency for Research Manages of EU Commission. Additionally, this research has been funded throught a research project (research project ULST-NANO) of the Proyectos Integradores MdM-IMEYMAT, call 2020, as well as the researcg project PID2020-118329RB-I00 funded by Spanish MCIN/AEI/10.13039/501100011033 action. Moreover, this research was also co-financed through two regional research projects funded by the Junta de Andalucía, specifically, the research project PECART-0096-2020 (Consejería Salud y Familias. JA Spain) and the research project P20_01293 (Consejería Economía, Conocimiento, Empresas y Universidad. JA Spain). In addition, Dr. Monserrat Llaguno-Munive is grateful for the funding received through the post-doctoral grant of the Consejo Nacional de Ciencia y Tecnología from Mexico (CONACYT, no 619639). In addition, we acknowledge the received technical assistance from the SC-ICYT of the University of Cádiz and the Servicio General de Apoyo a la Investigación-SAI, Universidad de Zaragoza. We also acknowledge to the Networking Research Centre on Bioengineering, Biomaterials, and Nanomedicine (CIBERBBN) (which is financed by the Instituto de Salud Carlos III (ISCIII) with assistance from the European Regional Development Fund (ERDF)) and the ICTS “NANBIOSIS”, specifically the FVPR/U20 (http://www.nanbiosis.es/portfolio/u20-in-vivo-experimentalplatform/) for providing access to the micro-CT. Finally, we want to thank the company LASING S.L. its technical support in the development of the NANO-GLAS laser system where the LA-PLA experiments were carried out.Peer reviewe

Scanning pulsed laser ablation in liquids: An alternative route to obtaining biocompatible YbFe nanoparticles as multiplatform contrast agents for combined MRI and CT imaging

Ytterbium ferrites are being used in many promising applications, such as visible-light photocatalysis, solar cells, magnetooptic devices, electro-magnetic equipment, etc., due to their fantastic ferroelectric and ferromagnetic properties. However, despite their good magnetic and radiopaque features, the use of ytterbium ferrites as multiplatform contrast agents in magnetic resonance imaging (MRI) and X-ray computed tomography (CT) is still under-developed. This is mainly due to difficulties in obtaining stable and biocompatible aqueous colloidal dispersions of ytterbium ferrite nanoparticles. In order to overcome this limitation, this work explores an eco-friendly method to directly synthesize such dispersions by liquid-assisted pulsed laser ablation of ytterbium ferrite massive targets. First, orthorhombic bulk YbFeO3 targets were obtained by a reaction-sintering method. Then, colloidal dispersions of nanoparticles were produced directly in both distilled water and ethanol by irradiating the bulk YbFeO3 targets with high-power infrared nanosecond lasers pulses. A battery of techniques has been used to characterize the as synthesized YbFeO3 targets and colloidal dispersions of YbFe nanoparticles to determine their composition, structure, magnetic properties, X-ray attenuation potentials, and colloidal properties. Moreover, the biocompatibility of the systems was also analysed by MTT cell viability assay. Results indicated that the use of distilled water as ablation medium yields colloidal dispersions consisted mainly of paramagnetic ytterbium ferrite nanoparticles. Contrarily, the use of ethanol as solvent leads to colloidal dispersions of polycrystalline nanoparticles with both ferromagnetic and paramagnetic behaviour, due to the coexistence, in each nanoparticle, of ytterbium ferrite, ytterbium oxide, and iron oxide crystalline phases. Both colloidal dispersions exhibit also high biocompatibility and suitable X-ray attenuation properties. Moreover, they show bio-safe hydrodynamic sizes (lower than 200 nm) with acceptable overall hydrodynamic polydispersity index values (under 0.4), being stable in water for several weeks. These results pave the way for the future evaluation of Yb–Fe based nanoparticles as multiplatform contrast agents in multimodal MRI and CT imaging