Iron-based nanostructures, whether environmental or synthetic, can infiltrate the human body and interact with cells due to their nanoscale dimensions. Some human cells, upon the internalization of iron oxide nanoparticles and their biodegradation, are capable of de novo biosynthesis of magnetic nanostructures. This process is evidenced by a transient loss and subsequent recovery of magnetic signal, a phenomenon termed "cellular re-magnetization". In this study, we explored the intracellular fate of four types of iron-based nanoparticles: maghemite (Massart), magnetite, cobalt ferrite, and ferrihydrite. They were internalized by human mesenchymal stem cells that were then cultured under both biodegradation and biosynthesis conditions. Transmission electron microscopy revealed structural modifications of all four nanoparticle types over time, indicating active processing by the cells. Under biodegradation conditions, the cells exhibited a progressive decrease in magnetic signal from day 0 to 21. In contrast, under biosynthesis conditions, magnetometry showed a drop in magnetic signal from day 0 to day 3/9 for maghemite, magnetite, and cobalt ferrite, followed by a signal recovery at day 9/21, consistent with the de novo biosynthesis of superparamagnetic structures. For ferrihydrite, initially paramagnetic, a weak superparamagnetic signal emerged on day 21 in cells under biosynthesis conditions. These results support the efficiency of the in vitro cell model, where cells internalize and degrade exogenous nanoparticles and reroute released iron to generate biogenic magnetic nanostructures.

Temperature plays a critical role in regulating body mechanisms and indicating inflammatory processes. Local temperature increments above 42 °C are shown to kill cancer cells in tumorous tissue, leading to the development of nanoparticle‐mediated thermo‐therapeutic strategies for fighting oncological diseases. Remarkably, these therapeutic effects can occur without macroscopic temperature rise, suggesting localized nanoparticle heating, and minimizing side effects on healthy tissues. Nanothermometry has received considerable attention as a means of developing nanothermosensing approaches to monitor the temperature at the core of nanoparticle atoms inside cells. In this study, a label‐free, direct, and universal nanoscale thermometry is proposed to monitor the thermal processes of nanoparticles under photoexcitation in the tumor environment. Gold‐iron oxide nanohybrids are utilized as multifunctional photothermal agents internalized in a 3D tumor model of glioblastoma that mimics the in vivo scenario. The local temperature under near‐infrared photo‐excitation is monitored by X‐ray absorption spectroscopy (XAS) at the Au L 3 ‐edge (11 919 eV) to obtain their temperature in cells, deepening the knowledge of nanothermal tumor treatments. This nanothermometric approach demonstrates its potential in detecting high nanothermal changes in tumor‐mimicking tissues. It offers a notable advantage by enabling thermal sensing of any element, effectively transforming any material into a nanothermometer within biological environments.

Iron is one of the most common metals in the human body, with an intrinsic metabolism including proteins involved in its transport, storage, and redox mechanisms. A less explored singularity is the presence of magnetic iron in the organism, especially in the brain. The capacity of human stem cells to biosynthesize magnetic nanoparticles was recently demonstrated, using iron released by the degradation of synthetic magnetic nanoparticles. To evidence a magnetic biomineralization in mammalian cells, it is required to address the biosynthesis of magnetic nanoparticles in cells supplied exclusively with non-magnetic iron salt precursors. Herein, mouse and human mesenchymal stem cells were incubated with ferric quinate for up to 36 days. By optimizing the concentration and culture time, and by measuring both total intracellular iron content and cellular magnetic signals, the biosynthesis of magnetic nanoparticles was found to occur from 14 days of continuous iron incubation and was correlated with important doses of intracellular iron. The local electronic structure and chemical environment of intracellular iron were further characterized by XAS spectroscopy at the Fe K-edge, showing a total conversion of Fe2+ to Fe3+ when using ferrous salts (ascorbate and sulfate), and a transformation towards ferrihydrite as well as a small proportion of a magnetic phase.

The combined passive and active targeting of tumoral tissue remains an active and relevant cancer research field. Here, we exploit the properties of two highly magnetic nanomaterials, magnetosomes and ultramagnetic liposomes, in order to magnetically target prostate adenocarcinoma tumors, implanted orthotopically or subcutaneously, to take into account the role of tumor vascularization in the targeting efficiency. Analysis of organ biodistribution in vivo revealed that, for all conditions, both nanomaterials accumulate mostly in the liver and spleen, with an overall low tumor retention. However, both nanomaterials were more readily identified in orthotopic tumors, reflecting their higher tumor vascularization. Additionally, a 2- and 3-fold increase in nanomaterial accumulation was achieved with magnetic targeting. In summary, ultramagnetic nanomaterials show promise mostly in the targeting of highly-vascularized orthotopic murine tumor models.

The Fe(II)-induced ferroptotic cell death pathway is an asset in cancer therapy, yet it calls into question the biocompatibility of magnetic nanoparticles. In the latter, Fe(II) is sequestered within the crystal structure and is released only upon nanoparticle degradation, a transition that is not well understood. Here, we dissect the chemical environment necessary for nanoparticle degradation and subsequent Fe(II) release. Importantly, temperature acts as an accelerator of the process and can be triggered remotely by laser-mediated photothermal conversion, as evidenced by the loss of the nanoparticles’ magnetic fingerprint. Remarkably, the local hot-spot temperature generated at the nanoscale can be measured in operando, in the vicinity of each nanoparticle, by comparing the photothermal-induced nanoparticle degradation patterns with those of global heating. Further, remote photothermal irradiation accelerates degradation inside cancer cells in a tumor spheroid model, with efficiency correlating with the endocytosis progression state of the nanoparticles. High-throughput imaging quantification of Fe 2+ release, ROS generation, lipid peroxidation and cell death at the spheroid level confirm the synergistic thermo-ferroptotic therapy due to the photothermal degradation at the nanoparticle level.

While gold-based nanoparticles are now commonly used in nanomedicine due to their stability and high plasmonic resonance, platinum nanoparticles are recently emerging as promising candidates for enhancing radiotherapy sensitivity due to their high atomic number. Here, we demonstrate that platinum-based nanomaterials with a multi-core structure also possess efficient near-infrared photothermal properties, despite platinum’s maximum absorption being primarily in the ultraviolet region. The photothermal efficacy of these platinum multi-core raspberry-like nanoparticles is compared with single-core ultra-small platinum nanoseeds, within glioblastoma cancer spheroids, showcasing the potential of platinum nanocore aggregation for photothermal therapy in cancer treatment. Additionally, we used a microfabrication technique for high-throughput growth of spheroids in microwells to evaluate photothermal treatment on glioblastoma spheroids. Finally, X-ray absorption spectroscopy was conducted to analyze the stability and behavior of both nanoparticles in the cellular environment, indicating their excellent biostability. Moreover, even after laser application, none of the nanoparticles degraded but instead underwent reshaping into a more crystalline structure.

Magnetic nanoparticles, made of iron oxide, present a peculiar interest for a wide range of biomedical applications for which they are often internalized in cells and then left within. One challenge is to assess their fate in the intracellular environment with reliable and precise methodologies. Herein, we introduce the use of the vibrating sample magnetometer (VSM) to precisely quantify the integrity of magnetic nanoparticles within cells by measuring their magnetic moment. Stem cells are first labeled with two types of magnetic nanoparticles; the nanoparticles have the same core produced via a fast and efficient microwave-based nonaqueous sol gel synthesis and differ in their coating: the commonly used citric acid molecule is compared to polyacrylic acid. The formation of 3D cell-spheroids is then achieved via centrifugation and the magnetic moment of these spheroids is measured at different times with the VSM. The obtained moment is a direct fingerprint of the nanoparticles' integrity, with decreasing values indicative of a nanoparticle degradation. For both nanoparticles, the magnetic moment decreases over culture time revealing their biodegradation. A protective effect of the polyacrylic acid coating is also shown, when compared to citric acid.

We designed monodisperse and perfectly shaped core/shell AuNP@Mo(4)Zol(2)Mn nanohybrids consisting of gold nanoparticles (AuNPs) functionalized by an antitumoral polyoxometalate (POM) incorporating the biologically active zoledronate ligand. After incubation, the nanoparticles were readily confined in the endosomal compartments of PC3 human prostate adenocarcinoma cells. Under photothermal treatment, the metabolic activity drastically decreased at concentrations where the nanohybrids exhibited no anticancer activity in the dark, and almost all cancer cells were killed at concentrations at which zoledronate alone was totally inactive. This study evidences for the first time that AuNPs capped by POMs can represent excellent candidates for combined chemotherapy and photothermal cancer therapy.

The use of magnetic nanoparticles in nanomedicine keeps expanding and,for most applications,the nanoparticles are internalized in cells then left within,bringing the need for accurate,fast,and easy to handle methodologies to assess their behavior in the cellular environment.Herein,a benchtop-size magnetic sensor is introduced to provide real-time precise measurement of nanoparticle magnetism within living cells.The values obtained with the sensor,of cells loaded with different doses of magnetic nanoparticles,are first compared to conventional vibrating sample magnetometry (VSM),and a strong correlation remarkably validates the use of the magnetic sensor as magnetometer to determine the nanoparticle cellular uptake.The sensor is then used to monitor the progressive intracellular degradation of the nanoparticles,over days.Importantly,this real-time in situ measure is performed on a stem cell-spheroid tissue model and can run continuously on a same spheroid,with cells kept alive within.Besides,such continuous magnetic measurement of cell magnetism at the tissue scale does not impact either tissue formation,viability,or stem cell function,including differentiation and extracellular matrix production.