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

Introducing Axial Chirality into Mesoionic 4,4′-Bis(1,2,3-triazole) Dicarbenes

Mesoionic 4,4′-bis(1,2,3-triazole-5,5′-diylidene) Rh(I) complexes having a C2 chiral 4,4′-axis were accessed from 3-alkyltriazolium salts in virtually complete de. Their structure and configurational integrity were assessed by NMR spectroscopy, X-ray crystallography, and chiral HPLC. Computational analysis of the MICs involved in the reaction suggested the formation of a highly stable and unprecedented cation-carbene intermediate species, which could be evidenced experimentally by cyclic voltammetry analysis

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

Triggering antitumoural drug release and gene expression by magnetic hyperthermia

Magnetic nanoparticles (MNPs) are promising tools for a wide array of biomedical applications. One of their most outstanding properties is the ability to generate heat when exposed to alternating magnetic fields, usually exploited in magnetic hyperthermia therapy of cancer. In this contribution, we provide a critical review of the use of MNPs and magnetic hyperthermia as drug release and gene expression triggers for cancer therapy. Several strategies for the release of chemotherapeutic drugs from thermo-responsive matrices are discussed, providing representative examples of their application at different levels (from proof of concept to in vivo applications). The potential of magnetic hyperthermia to promote in situ expression of therapeutic genes using vectors that contain heat-responsive promoters is also reviewed in the context of cancer gene therapy

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

Effect of surface chemistry and associated protein corona on the long-term biodegradation of iron oxide nanoparticles in Vivo

The protein corona formed on the surface of a nanoparticle in a biological medium determines its behavior in vivo. Herein, iron oxide nanoparticles containing the same core and shell, but bearing two different surface coatings, either glucose or poly(ethylene glycol), were evaluated. The nanoparticles' protein adsorption, in vitro degradation, and in vivo biodistribution and biotransformation over four months were investigated. Although both types of nanoparticles bound similar amounts of proteins in vitro, the differences in the protein corona composition correlated to the nanoparticles biodistribution in vivo. Interestingly, in vitro degradation studies demonstrated faster degradation for nanoparticles functionalized with glucose, whereas the in vivo results were opposite with accelerated biodegradation and clearance of the nanoparticles functionalized with poly(ethylene glycol). Therefore, the variation in the degradation rate observed in vivo could be related not only to the molecules attached to the surface, but also with the associated protein corona, as the key role of the adsorbed proteins on the magnetic core degradation has been demonstrated in vitro

Quantification of Lipoprotein Uptake in Vivo Using Magnetic Particle Imaging and Spectroscopy

Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake in vivo has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of in vivo uptake of chylomicrons, the primary carriers of dietary lipids, in metabolically active tissues using magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS). We show that loading artificial chylomicrons (ACM) with iron oxide nanoparticles (IONPs) enables rapid and highly sensitive post hoc detection of lipid uptake in situ using MPS. Importantly, by utilizing highly magnetic Zn-doped iron oxide nanoparticles (ZnMNPs), we generated ACM with MPI tracer properties superseding the current gold-standard, Resovist, enabling quantification of lipid uptake from whole-animal scans. We focused on brown adipose tissue (BAT), which dissipates heat and can consume a large part of nutrient lipids, as a model for tightly regulated and inducible lipid uptake. High BAT activity in humans correlates with leanness and improved cardiometabolic health. However, the lack of nonradioactive imaging techniques is an important hurdle for the development of BAT-centered therapies for metabolic diseases such as obesity and type 2 diabetes. Comparison of MPI measurements with iron quantification by inductively coupled plasma mass spectrometry revealed that MPI rivals the performance of this highly sensitive technique. Our results represent radioactivity-free quantification of lipid uptake in metabolically active tissues such as BAT

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