Influence of magnetic nanoparticle degradation in the frame of magnetic hyperthermia and photothermal treatments

This work aims at studying how the transformations that magnetic nanoparticles suffer in vivo affect their heating properties in the frame of hyperthermia treatments. Iron oxide magnetic nanoparticles (≈13 nm) with two different coatings [PMAO (polymaleic anhydride-alt-1-octadecene) and DMSA (dimercaptosuccinic acid)] have been subjected to an accelerated degradation in a medium simulating lysosome conditions. The particles physicochemical properties (size, size distribution, and magnetic properties) have been followed over the degradation process along 24 days. It was found that DMSA-coated particles degraded much faster than PMAO-coated ones. In addition, their heating properties under both the exposure to an alternating magnetic field or a near infrared light have been tracked along this degradation processes, assessing how the changes in their physicochemical properties affect their heating capacity. Along the degradation procedure, a stronger decrease of the particles heating properties has been observed in the frame of magnetic hyperthermia measurements, in comparison with the photothermal ones. Finally, the PMAO-coated particles have been selected for a degradation study in vivo after intratumoral administration. Interestingly, although the number of particles decreases with time in the tissue, the size and size distribution of the particles do not change significantly over time. This work is especially relevant in the frame of the design of in vivo hyperthermia treatments using magnetic nanoparticles as it would provide fundamental clues regarding the need of repeated doses or the possible use of a single administration depending on the treatment duration

Membrane-localized magnetic hyperthermia promotes intracellular delivery of cell-impermeant probes

Funding Information: This work was supported by the following grants: AEI, Grant PCIN-2017-060 funded by MICIU/AEI/10.13039/501100011033 and co-funded by the European Union (M-ERA.NET COFUND call 2016), grants PGC2018-096016-B-I00 to R. M. F and BIO 2017-84246-C2-1R to V. G. and J. M. F. funded by MICIU/AEI/10.13039/501100011033 and by \u201CERDF A way of making Europe\u201D, grant RYC2015-17640 to R. M. F. and RYC2019-026860-I to M. M. funded by MICIU/AEI/10.13039/501100011033 and by \u201CESF Investing in your future\u201D, and grant CNS2023-144436 funded by MICIU/AEI/10.13039/501100011033 and by \u201CEuropean Union Next Generation EU/PRTR\u201D. This work was also financed by national funds from FCT \u2013 Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia, I. P., in the scope of the project project M-ERA.NET2/0008/2016. J. I. L. acknowledges financial support for his predoctoral fellowships from Gobierno de Arag\u00F3n (DGA 2017-2021 call, co-funded by the Programa Operativo Fondo Social Europeo de Arag\u00F3n 2014\u20132020). L. A. acknowledges support from the Jos\u00E9 Castillejo program (CAS18/00233). The authors also acknowledge support from Gobierno de Arag\u00F3n and Fondos Feder for funding the Bionanosurf (E15_23R) research group. The authors would like to acknowledge the use of Servicios Cientif\u00EDcos T\u00E9cnicos del CIBA (IACS-Universidad de Zaragoza), the Advanced Microscopy Laboratory (Universidad de Zaragoza), for access to their instrumentation and expertise and for the use of Servicio General de Apoyo a la Investigaci\u00F3n-SAI, Universidad de Zaragoza, BIOLAB@UCIBIO, NOVA School of Science and Technology for flow cytometry experiments. We also thank Eduardo Moreno-Antol\u00EDn (Bionanosurf group, INMA, UNIZAR-CSIC) for insightful discussions and help with the preparation of the MNPs. Publisher Copyright: © 2024 The Royal Society of Chemistry.In this work, we report the disruptive use of membrane-localized magnetic hyperthermia to promote the internalization of cell-impermeant probes. Under an alternating magnetic field, magnetic nanoparticles (MNPs) immobilized on the cell membrane via bioorthogonal click chemistry act as nanoheaters and lead to the thermal disruption of the plasma membrane, which can be used for internalization of different types of molecules, such as small fluorescent probes and nucleic acids. Noteworthily, no cell death, oxidative stress and alterations of the cell cycle are detected after the thermal stimulus, although cells are able to sense and respond to the thermal stimulus through the expression of different types of heat shock proteins (HSPs). Finally, we demonstrate the utility of this approach for the transfection of cells with a small interference RNA (siRNA), revealing a similar efficacy to a standard transfection method based on the use of cationic lipid-based reagents (such as Lipofectamine), but with lower cell toxicity. These results open the possibility of developing new procedures for “opening and closing” cellular membranes with minimal disturbance of cellular integrity. This on-demand modification of cell membrane permeability could allow the direct intracellular delivery of biologically relevant (bio)molecules, drugs and nanomaterials, thus overcoming traditional endocytosis pathways and avoiding endosomal entrapment.publishersversionpublishe

Fate and transformation of silver nanoparticles in different biological conditions

The exploitation of silver nanoparticles (AgNPs) in biomedicine represents more than one third of their overall application. Despite their wide use and significant amount of scientific data on their effects on biological systems, detailed insight into their in vivo fate is still lacking. This study aimed to elucidate the biotransformation patterns of AgNPs following oral administration. Colloidal stability, biochemical transformation, dissolution, and degradation behaviour of different types of AgNPs were evaluated in systems modelled to represent biological environments relevant for oral administration, as well as in cell culture media and tissue compartments obtained from animal models. A multimethod approach was employed by implementing light scattering (dynamic and electrophoretic) techniques, spectroscopy (UV–vis, atomic absorption, nuclear magnetic resonance) and transmission electron microscopy. The obtained results demonstrated that AgNPs may transform very quickly during their journey through different biological conditions. They are able to degrade to an ionic form and again reconstruct to a nanoparticulate form, depending on the biological environment determined by specific body compartments. As suggested for other inorganic nanoparticles by other research groups, AgNPs fail to preserve their specific integrity in in vivo settings

Synthesis of type II beta-turn surrogate dipeptides based on syn-alfa-amino-alfa, beta-dialkyl-beta-lactams

The achiral bis(trimethylsilyl)methyl group acts as an efficient stereochemical determinant of the α-alkylation reaction in β-branched α-phenyloxazolidinyl- or α-diphenyloxazolidinyl-β-lactams and provides the first stereocontrolled access to syn-α-amino-α,β-dialkyl(aryl)-β-lactams. These products are readily transformed into type II β-turn mimetic surrogates 2B.This work was supported by Spanish Ministerio de Educación y Ciencia (MEC; Project BQU2002-01737). Grants from Gobierno Vasco to A.B. and I.L. and from European Commission (Marie Curie HMPT-CT-2000-00173) to R.M.F., A.M., and K.R.P. are acknowledged.Peer reviewe

Synthesis of type II beta-turn surrogate dipeptides based on syn-alfa-amino-alfa, beta-dialkyl-beta-lactams. Supporting Information

Preparation procedures and physical and spectroscopic data for compounds 17−43 and crystallographic data in CIF format and ORTEP diagrams of 28 and 30.Peer reviewe

From monomeric to multimeric His-tag proteins conjugation to magnetic nanoparticles through NTA-Me2+: shape and size effects

Resumen del póster presentado a la 4th Spanish Conference on Biomedical Applications of Nanomaterials, celebrda online del 2 al 4 de junio de 2021.Peer reviewe

Dependence of intracellular magnetic nanoparticles amount in the apoptotic death pathway triggered by magnetic hyperthermia treatment

Trabajo presentado a la 4th Spanish Conference on Biomedical Applications of Nanomaterials, celebrada online del 2 al 4 de junio de 2021.Peer reviewe

Reversible Alignment of Nanoparticles and Intracellular Vesicles During Magnetic Hyperthermia Experiments

Heating magnetic nanoparticles (MNPs) with AC (Alternating Current) magnetic fields has received significant attention in recent years, particularly for biomedical uses. However, most studies focus on characterizing the heat release, overlooking the fact that the MNPs in the viscous cell environment constitute a dynamic magnetic colloid whose configuration may evolve over time, particularly if a driving force as the AC field is applied. Aiming to shed light on this matter, in this workthe dynamics of the colloid structure during hyperthermia experiments are studied. By combining various experimental and theoretical tools, it is concluded that the AC field may drive the formation of aligned structures, and the impact that such structures may have on the associated heating is assessed. Remarkably, the results show that those field‐driven structures are highly unstable for small particle sizes, rapidly disassembling upon field removal. Moreover, an analogous behavior in vitro is found, with the AC magnetic field also promoting a reversible alignment of vesicles containing the MNPs within the cells. The results suggest that the observed alignment, both of MNPs and intracellular vesicles, may be a common phenomenon in usual hyperthermia experiments, but unnoticed because of the intrinsic unstable nature of the aligned structures

Synthesis and functionalization of magnetic nanoparticles for magnetic hyperthermia applications

Resumen del trabajo presentado al Molecular Horizons Seminar de la University of Wollongong (Australia) celebrado el 3 de octubre de 2019