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

A device-independent approach to evaluate the heating performance during magnetic hyperthermia experiments: peak analysis and zigzag protocol

Accurate knowledge of the heating performance of magnetic nanoparticles (MNPs) under AC fields is critical for the development of hyperthermia-mediated applications. Usually reported in terms of the specific loss power (SLP) obtained from the temperature variation ($\Delta{T}$) vs. time (t) curve, such estimate is subjected to a huge uncertainty. Thus, very different SLP values are reported for the same particles when measured on different equipment/laboratories. This lack of control clearly hampers the further development of MNP-mediated heat-triggered technologies. Here we report a device-independent approach to calculate the SLP value of a suspension of MNPs: the SLP is obtained from the analysis of the peak at the field on/off switch of the $\Delta{T}(t)$ curve. The measurement procedure, which itself constitutes a change of paradigm within the field, is based on fundamental physics considerations: specifically to guarantee the applicability of Newton's law of cooling, as i) it corresponds to the ideal scenario in which the temperature profiles of the system during heating and cooling are the same; and ii) it diminishes the role of coexistence of various heat dissipation channels. Such an approach is supported by theoretical and computational calculations to increase the reliability and reproducibility of SLP determination. This is experimentally confirmed, demonstrating a reduction in SLP variation across 3 different devices located in 3 different laboratories. Furthermore, the application of this peak analysis method (PAM) to a rapid succession of field on/off switches that result in a zigzag-like $\Delta{T}(t)$, which we term the zigzag protocol, allows evaluating possible variations of the SLP values with time or temperature.Comment: main text: 30 pages, 9 figure

Iron–Gold Nanoflowers: A Promising Tool for Multimodal Imaging and Hyperthermia Therapy

The development of nanoplatforms prepared to perform both multimodal imaging and combined therapies in a single entity is a fast-growing field. These systems are able to improve diagnostic accuracy and therapy success. Multicomponent Nanoparticles (MCNPs), composed of iron oxide and gold, offer new opportunities for Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) diagnosis, as well as combined therapies based on Magnetic Hyperthermia (MH) and Photothermal Therapy (PT). In this work, we describe a new seed-assisted method for the synthesis of Au@Fe Nanoparticles (NPs) with a flower-like structure. For biomedical purposes, Au@Fe NPs were functionalized with a PEGylated ligand, leading to high colloidal stability. Moreover, the as-obtained Au@Fe-PEG NPs exhibited excellent features as both MRI and CT Contrast Agents (CAs), with high r2 relaxivity (60.5 mM−1⋅s−1) and X-ray attenuation properties (8.8 HU mM−1⋅HU). In addition, these nanoflowers presented considerable energy-to-heat conversion under both Alternating Magnetic Fields (AMFs) (∆T ≈ 2.5 °C) and Near-Infrared (NIR) light (∆T ≈ 17 °C). Finally, Au@Fe-PEG NPs exhibited very low cytotoxicity, confirming their potential for theranostics applications.Spanish Ministry of Economy, Industry and Competitiveness CTQ2017-86655-RSpanish Ministry of Science and Innovation PID2020-118448RB-C21Spanish Ministry of Science and Innovation PID2020-113108RB-I00MCIN/AEI/10.13039/501100011033Fondo Social de la DGA (grupos DGA) PGC2018-096016-B-I00Regional Ministry of Health of Andalusia OH-0026-2018Regional Ministry of Health of Andalusia PAIDI 2020. P20_0072

Beyond Newton's law of cooling in evaluating magnetic hyperthermia performance: a device-independent procedure †

Accurate knowledge of the heating performance of magnetic nanoparticles (MNPs) under AC magnetic fields is critical for the development of hyperthermia-mediated applications. Usually reported in terms of the specific loss power (SLP) obtained from the temperature variation (ΔT) vs. time (t) curve, such an estimate is subjected to a huge uncertainty. Thus, very different SLP values are reported for the same particles when measured on different equipment/in different laboratories. This lack of control clearly hampers the further development of nanoparticle-mediated heat-triggered technologies. Here, we report a device-independent approach to calculate the SLP value of a suspension of magnetic nanoparticles: the SLP is obtained from the analysis of the peak at the AC magnetic field on/off switch of the ΔT(time) curve. The measurement procedure, which itself constitutes a change of paradigm within the field, is based on the heat diffusion equation, which is still valid when the assumptions of Newton's law of cooling are not applicable, as (i) it corresponds to the ideal scenario in which the temperature profiles of the system during heating and cooling are the same; and (ii) it diminishes the role of coexistence of various heat dissipation channels. Such an approach is supported by theoretical and computational calculations to increase the reliability and reproducibility of SLP determination. Furthermore, the new methodological approach is experimentally confirmed, by magnetic hyperthermia experiments performed using 3 different devices located in 3 different laboratories. Furthermore, the application of this peak analysis method (PAM) to a rapid succession of stimulus on/off switches which results in a zigzag-like ΔT(t), which we term the zigzag protocol, allows evaluation of possible variations of the SLP values with time or temperature

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

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

Ultrasmall manganese ferrites for in vivo catalase mimicking activity and multimodal bioimaging

Manganese ferrite nanoparticles display interesting features in bioimaging and catalytic therapies. They have been recently used in theranostics as contrast agents in magnetic resonance imaging (MRI), and as catalase-mimicking nanozymes for hypoxia alleviation. These promising applications encourage the development of novel synthetic procedures to enhance the bioimaging and catalytic properties of these nanomaterials simultaneously. Herein, a cost-efficient synthetic microwave method is developed to manufacture ultrasmall manganese ferrite nanoparticles as advanced multimodal contrast agents in MRI and positron emission tomography (PET), and improved nanozymes. Such a synthetic method allows doping ferrites with Mn in a wide stoichiometric range (MnxFe3-xO4, 0.1 ≤ x ≤ 2.4), affording a library of nanoparticles with different magnetic relaxivities and catalytic properties. These tuned magnetic properties give rise to either positive or dual-mode MRI contrast agents. On the other hand, higher levels of Mn doping enhance the catalytic efficiency of the resulting nanozymes. Finally, through their intracellular catalase-mimicking activity, these ultrasmall manganese ferrite nanoparticles induce an unprecedented tumor growth inhibition in a breast cancer murine model. All of these results show the robust characteristics of these nanoparticles for nanobiotechnological applications.The authors thank M. Jeannin from Lasie Laboratory (La Rochelle University) for the Raman studies. S.C.R. is supported by the grant PID2019-106139RA-100 funded by MCIN. J.R.-C. is supported by grants from the Ministerio de Economía, Industria y Competitividad (MEIC) (SAF2017-84494-C2-R). J.R.C. received funding from the BBVA Foundation (PR [18]_BIO_IMG_0008) and La Caixa (HR18-00052). Y.F.-A. received funding from the Santander-Universidad Zaragoza Fellowship program. L.G. acknowledges financial support from the Ramón y Cajal program (RYC-2014-15512). CIC biomaGUNE is supported by the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (MDM-2017-0720). The authors acknowledge the use of Servicio General de Apoyo a la Investigación-SAI, Universidad de Zaragoza. H.G. is supported by the Ligue contre le Cancer (CD16, CD17) and Région Nouvelle Aquitaine (Projet “Nanovect”). J.A.E. is supported by RTI2018-099357-B-I00, HFSP (RGP0016/2018), CIBERFES16/10/00282 and RED2018-102576-T. The CNIC is supported by the Pro-CNIC Foundation and by the Severo Ochoa of Excellence Program.Peer reviewe

Magnetic nanoparticle transformations and the effect of their heating properties

Resumen del trabajo presentado a la 13th International Conference on the Scientific and Clinical Applications of Magnetic Carriers, celebrada en London (UK) del 14 al 17 de junio de 2022.Peer reviewe

Evaluation of the properties and heating capacity of the magnetic nanoparticles during degradation process

Trabajo presentado a la Conference on Advanced Materials and Devices for Nanomed (AMA4MED), celebrada en Valencia (España) del 3 al 4 de mayo de 2022.Peer reviewe

Magnetic nanoparticle transformations and the effect on their heating properties

Resumen del trabajo presentado a la 5th Spanish Conference on Biomedical Applications of Nanomaterials (SBAN), celebrada on-line del 3 al 10 de septiembre de 2022.N