A New Capillary-Channel Agarose Sponge Assembled with Deep Eutectic Solvent Based Magnetic Fluid for Rapid Hemostasis and Prevention of Bacterial Infection.

A new composite sponge assisted by magnetic field-mediated guidance was developed for effective hemostasis. It was based on polydopamine capillary-channel agarose (PDA-CAGA) sponge as matrix; meanwhile, the combination of deep eutectic solvent (DES, choline chloride:glycerol = 1:1, M/M)-dispersed Fe3O4 nanoparticles after fabrication by tannic acid (DES-Fe3O4@TA) was applied as hemostatic magnetic fluid. This sponge had oriented and aligned capillary channels realized by a 3D printed pattern, which endowed them with obvious shape memory and liquid absorption performance. Computational simulation was performed to describe the fluid status in channels; DES-Fe3O4@TA exhibited good magnetic properties, fluidity, and stability. In addition, the sponge driven to react rapidly with the bleeding site under the effect of a magnetic field presented a shorter hemostasis time (reduced by 85.02% in the tail and 81.07% in the liver of rats) and less blood loss (reduced by 97.08% in the tail and 91.50% in the liver) than those of medical gelatin sponge (GS). Meanwhile, the multifunctional material also exhibited better biocompatibility, procoagulant performance, and significant inhibition on S. aureus and E. coli than GS. As a whole, this work proposed a new strategy for rapid hemostasis by designing a magnetic field assisted composite bacteriostatic material, which also expanded the applications of green solvents in the clinical management field.

Integrable Magnetic Fluid Hyperthermia Systems for 3D Magnetic Particle Imaging.

Background: Combining magnetic particle imaging (MPI) and magnetic fluid hyperthermia (MFH) offers the ability to perform localized hyperthermia and magnetic particle imaging-assisted thermometry of hyperthermia treatment. This allows precise regional selective heating inside the body without invasive interventions. In current MPI-MFH platforms, separate systems are used, which require object transfer from one system to another. Here, we present the design, development and evaluation process for integrable MFH platforms, which extends a commercial MPI scanner with the functionality of MFH. Methods: The biggest issue of integrating magnetic fluid hyperthermia platforms into a magnetic particle imaging system is the magnetic coupling of the devices, which induces high voltage in the imaging system, and is harming its components. In this paper, we use a self-compensation approach derived from heuristic algorithms to protect the magnetic particle imaging scanner. The integrable platforms are evaluated regarding electrical and magnetic characteristics, cooling capability, field strength, the magnetic coupling to a replica of the magnetic particle imaging system's main solenoid and particle heating. Results: The MFH platforms generate suitable magnetic fields for the magnetic heating of particles and are compatible with a commercial magnetic particle imaging scanner. In combination with the imaging system, selective heating with a gradient field and steerable heating positioning using the MPI focus fields are possible. Conclusion: The proposed MFH platforms serve as a therapeutic tool to unlock the MFH functionality of a commercial magnetic particle imaging scanner, enabling its use in future preclinical trials of MPI-guided, spatially selective magnetic hyperthermia therapy.

An agent-based model for studying the temperature changes on environments exposed to magnetic fluid hyperthermia.

Magnetic fluid hyperthermia (MFH) is a technique whose results show promise in the treatment against cancer, but which still faces obstacles such as controlling the spatial distribution of temperature. The present study developed an agent-based model in order to simulate the temperature changes in an aqueous environment submitted to the magnetic fluid hyperthermia technique. The developed model was built with its parameters based on the clinical treatment protocol for glioblastoma multiforme (GBM). Using thermodynamic properties of magnetic fluid and tissues, we define a specific thermal parameter (α) and evaluate its influence, together with the intensity of the external magnetic field (H), on the dynamics of the temperature of the cancer environment. The temperature evolution generated by the model was in accordance with experimental results known from the subject literature. The parameters evaluation indicates that the temperature stabilization of the tumor environment during MFH treatment is due to the local interactions of energy diffusion, as well as indicating that the α-parameter is a key factor for controlling the temperature and heating speed.

Preparation of smart magnetic fluids and application in sewage treatment: Copper adsorption, kinetic and isotherm study.

The effective removal of heavy metal ions from sewage remains a critical issue, and applying the operability of magnetic materials to large volume wastewater treatment has been a significant challenge. In this paper, metal ions adsorption induced aggregation strategy is proposed to solve this contradiction. The intelligent magnetic fluid designed in this study is a well-dispersed fluid state when treating sewage, and can efficiently adsorb heavy metal ions in wastewater with high adsorption capacity and ultra-fast adsorption kinetics. More importantly, after saturation of adsorption, the magnetic fluid will transform from a well-dispersed fluid state to an agglomeration state which is easy to precipitate and separate via external magnetic field. In a simple and effective way, the particles size of magnetic nanoparticles was precisely controlled by cellulose derivatives modification to obtain a stable magnetic fluid in water. The Freundlich model best described Cu2+ adsorption on magnetite nanoparticles, the correlation coefficients from the Cu2+ adsorption on the two magnetic fluids are 0.9554 and 0.9336, n are 1.868 and 2.117, revealing a favorable adsorption of Cu2+ onto magnetic fluids. The pseudo second-order model fitted the adsorption kinetic data better, the qe are 0.1948 and 0.1315 mmol/g and the R2 are 0.9999, indicating that the adsorption of Cu2+ onto the magnetic fluid was dominated by chemisorption. Moreover, the removal rate of Cu2+ in tap water and lake water was more than 97.1%, and the removal rate of large volume sewage was 81.7%. The synthetic magnetic fluid has high adsorption capacity, ultra-fast adsorption kinetics, reusability and easy separation, indicating its potential application for the removal of heavy metal ions from large-volume sewage.

An Intensity-Demodulated Fiber-Optic Magnetometer Based on Nanostructured Magnetic Fluid-Filled Fluidic Photonic Crystal Fibers.

An intensity-demodulated fiber-optic magnetometer is proposed and experimentally investigated, which is fabricated via fusion splicing a segment of photonic crystal fiber (PCF) between single-mode fibers (SMFs), with the cladding air holes of PCF filled with magnetic fluid. Using the magneto-optical properties of the magnetic fluid, the transmission spectrum is changed with an external magnetic field. Based on the intensity variations in the transmission spectrum, the magnetic field is detected, and a sensitivity of 0.238 dB/mT is obtained at 1550.03 nm with the length of PCF 5.5 cm. By converting light signals into electrical signals, a sensitivity of 0.003 V/mT is achieved. The fiber-optic magnetometer possesses the advantages of simple fabrication, compact/robust structure, and low cost.

A nudge over the relaxation plateau: effect of pH, particle concentration, and medium viscosity on the AC induction heating efficiency of biocompatible chitosan-coated Fe3O4nanoparticles.

The effects of pH, MNP concentration, and medium viscosity on the magnetic fluid hyperthermia (MFH) properties of chitosan-coated superparamagnetic Fe3O4nanoparticles (MNPs) are probed here. Due to the protonation of the amide groups, the MNPs are colloidally stable at lower pH (∼2), but form aggregates at higher pH (∼8). The increased aggregate size at higher pH causes the Brownian relaxation time (τB) to increase, leading to a decrease in specific absorption rate (SAR). For colloidal conditions ensuring Brownian-dominated relaxation dynamics, an increase in MNP concentrations or medium viscosity is found to increase theτB. SAR decreases with increasing MNP concentration, whereas it exhibits a non-monotonic variation with increasing medium viscosity. Dynamic hysteresis loop-based calculations are found to be in agreement with the experimental results. The findings provide a greater understanding of the variation of SAR with the colloidal properties and show the importance of relaxation dynamics on MFH efficiency, where variations in the frequency-relaxation time product across the relaxation plateau cause significant variations in SAR. Further, thein vitrocytotoxicity studies show good bio-compatibility of the chitosan-coated Fe3O4MNPs. Higher SAR at acidic pH for bio-medically acceptable field parameters makes the bio-compatible chitosan-coated Fe3O4MNPs suitable for MFH applications.

In situ theranostic platform combining highly localized magnetic fluid hyperthermia, magnetic particle imaging, and thermometry in 3D.

Theranostic platforms, combining diagnostic and therapeutic approaches within one system, have garnered interest in augmenting invasive surgical, chemical, and ionizing interventions. Magnetic particle imaging (MPI) offers a quite recent alternative to established radiation-based diagnostic modalities with its versatile tracer material (superparamagnetic iron oxide nanoparticles, SPION). It also offers a bimodal theranostic framework that can combine tomographic imaging with therapeutic techniques using the very same SPION. Methods: We show the interleaved combination of MPI-based imaging, therapy (highly localized magnetic fluid hyperthermia (MFH)) and therapy safety control (MPI-based thermometry) within one theranostic platform in all three spatial dimensions using a commercial MPI system and a custom-made heating insert. The heating characteristics as well as theranostic applications of the platform were demonstrated by various phantom experiments using commercial SPION. Results: We have shown the feasibility of an MPI-MFH-based theranostic platform by demonstrating high spatial control of the therapeutic target, adequate MPI-based thermometry, and successful in situ interleaved MPI-MFH application. Conclusions: MPI-MFH-based theranostic platforms serve as valuable tools that enable the synergistic integration of diagnostic and therapeutic approaches. The transition into in vivo studies will be essential to further validate their potential, and it holds promising prospects for future advancements.

Inversion of magnetic diameter distribution of magnetic fluids under high and low temperatures.

The magnetic diameter is a crucial factor affecting the magnetic properties of magnetic fluids. The magnetic diameter distribution can be estimated based on the magnetic properties. However, the magnetic dipole interaction of magnetic nanoparticles (MNPs) and the variation of the magnetic diameter with temperature have received relatively little attention in previous research. Hence, this research proposes the AP-MMF1-L method to inverse the magnetic diameter which considers the magnetic dipole interaction and derives the magnetic diameter at different temperatures. Firstly, the AP-MMF1-L uses the least square method between the first-order modified mean-field Langevin function (MMF1-L) and the measured magnetization curve as the objective function. Meanwhile, the hybrid Artificial bee colony-particle swarm (AP) optimization algorithm is introduced to inverse the optimal magnetic diameter distribution. Secondly, the hydrodynamic diameter distribution experimental values are compared with the theoretical values, demonstrating the AP-MMF1-L method obtains accurate inversion results of the magnetic diameter distribution when compared to other models. Finally, the arithmetic mean of the magnetic diameter at different temperatures is investigated, revealing a decreasing trend as the temperature rises, approximately following a linear distribution. The AP-MMF1-L provides a novel and effective tool for accurately determining the magnetic diameter of the MNPs across various temperatures.

2D-Vector Magnetic Sensing Based on Ring-Shaped Fiber-Optic Structure Coated with Magnetic Fluid.

In this work, a novel fiber-optic sensor for 2D magnetic sensing is explored based on nanostructured magnetic fluid. The fiber-optic sensor comprises a ring-shaped fiber structure that is coated with magnetic fluid. The unique magneto-optical characteristic of the nanostructured magnetic fluid enables the fiber-optic structure to detect magnetic fields. By utilizing the 3D Monte Carlo method, the magneto-optical characteristic induced by the nanostructure changes in the magnetic fluid was analyzed. The sensor can realize 2D vector magnetic sensing by intensity demodulation and achieves a sensitivity of 2.402 dB/mT. The proposed fiber optic sensor helps in developing a high-sensitivity 2D vector magnetic field sensor, which has potential applications in the fields of navigation, electrical power systems, and biological detection.

Experimental Study on Thermal Conductivity of Water-Based Magnetic Fluid Loaded with Different Nanoparticles.

Magnetic fluids, a new type of energy transfer fluid with tunable properties, have garnered significant interest from researchers worldwide. Hybrid magnetic fluids prepared by adding different types of nanoparticles exhibit superior thermophysical properties and functional characteristics. In this paper, we prepared a water-based magnetic fluid loaded with multi-walled carbon nanotubes (MCNTs), silver (Ag), and copper (Cu) to enhance thermal conductivity. Using a transient double hot-wire method, we designed and built an experimental measurement system for the thermal conductivity of magnetic fluids with an average measurement error of less than 5%. We studied the thermal conductivity of hybrid magnetic fluids under different conditions and evaluated the advantages and disadvantages of various models, including the Maxwell model, H&C model, Tim model, Y&C model, and Evans model. Our results show that MF+MCNTs, MF+Ag, and MF+Cu nanofluids can all improve the thermal conductivity of the carrier fluid, with MF+MCNTs exhibiting the best improvement effect of 10.93%. Among the five models evaluated, the Evans model had the best predictive effect with a deviation range within 5%. This work provides theoretical and practical reference for enhancing the thermal conductivity of magnetic fluids and provides a more accurate theoretical model for calculating the thermal conductivity of hybrid magnetic fluids.

Magnetic Particle Imaging-Guided Hyperthermia for Precise Treatment of Cancer: Review, Challenges, and Prospects.

Magnetic particle imaging (MPI) is a novel quantitative imaging technique using the nonlinear magnetization behavior of magnetic nanoparticles (MNPs) to determine their local concentration. Magnetic fluid hyperthermia (MFH) is a promising non-invasive therapy using the heating effects of MNPs. MPI-MFH is expected to enable real-time MPI guidance, localized MFH, and non-invasive temperature monitoring, which shows great potential for precise treatment of cancer. In this review, we introduce the fundamentals of MPI and MFH and their applications in the treatment of cancer. Also, we discuss the challenges and prospects of MPI-MFH.

A Magnetic Field Sensor Based on Directional Coupling in a Magnetic Fluid-Filled Photonic Crystal Fiber.

In this paper, a dual-core photonic crystal fiber (DC-PCF) sensitivity sensor filled with magnetic liquid is introduced and investigated with the finite element method (FEM). To regulate the energy coupling involving the two cores, the magnetic fluid is filled into the pore between the two cores. To adjust the coupling between the supermodes in the DC-PCF, the refractive index (RI) of the air hole filled magnetic fluid may change due to the external magnetic field. This specifically created a magnetic fluid-filled DC-PCF; the magnetic fluid-filled hole is not used as the core for energy transmission, thus avoiding transmission loss. The dip wavelength and the magnetic field displayed an excellent linear connection between 80 and 260 Oe, depending on the numerical data. The detection sensitivity of the magnetic field reached 515.75 pm/Oe at a short fiber length of 482 µm. The designed magnetic fluid-filled DC-PCF has high sensitivity and small volume and has great application prospects in magnetic field detection in the medical and industrial fields.

Magnetically controlled drug delivery and hyperthermia effects of core-shell Cu@Mn3O4 nanoparticles towards cancer cells in vitro.

Recent increase in the integration of nanotechnology and nanosciences to the biomedical sector fetches the human wellness through the development of sustainable treatment methodologies for cancerous tumors at all stages of their initiation and progression. This involves the development of multifunctional theranostic probes that effectively support for the early cancer diagnosis, avoiding non-target cell toxicity, controlled and customized anticancer drug release etc. Therefore, to advance the field of nanotechnology-based sustainable cancer treatment, we fabricated and tested the efficacy of anticancer drug-loaded magnetic hybrid nanoparticles (NPs) towards in vitro cell culture systems. The developed conjugate of NPs was incorporated with the functions of both controlled drug delivery and heat-releasing ability using Mn3O4 (manganese oxide) magnetic core with Cu shell encapsulated within trimethyl chitosan (TMC) biopolymer. On characterization, the Cu@Mn3O4-TMC NPs were confirmed to have an approximate size of 130 nm with full agglomeration (as observed by the HRTEM) and crystal size of 92.95 ± 18.38 nm with tetragonal hausmannite phase for Mn3O4 spinel structure (XRD). Also, the UV-Vis and FTIR analysis provided the qualitative and quantitative effects of 5-fluororacil (5-Fu) anticancer drug loading (max 68 %) onto the Cu@Mn3O4-TMC NPs. The DLS analysis indicated for the occurrence of no significant changes to the particle size (around 100 nm) of Cu@Mn3O4-TMC due to the solution dispersion thereby confirming for the aqueous stability of developed NPs. In addition, the magnetization values of Cu@Mn3O4-TMC NPs were measured to be 34 emu/g and a blocking temperature of 42 K. Further tests of magnetic hyperthermia by the Cu@Mn3O4-TMC/5-Fu NPs provided that the heat-releasing capacity (% ΔT at 15 min) increases with that of increased frequency, i.e. 28 % (440 Hz) > 22.6 % (240 Hz) > 18 % (44 Hz), and the highest specific power loss (SPL) value observed to be 488 W/g for water. Moreover, the 5-Fu drug release studies indicate that the release is high at a pH of 5.2 and almost all the loaded drug is getting delivered under the influence of the external magnetic field (430 Hz) due to the influence of both Brownian-rotation and Néel relaxation heat-mediated mechanism. The pharmacokinetic drug release studies have suggested for the occurrence of more than one model, i.e. First-order, Higuchi (diffusion), and Korsemeyer-Peppas (non-Fickian), in addition to hyperthermia. Finally, the in vitro cell culture systems (MCF-7 cancer and MCF-10 non-cancer) helped to differentiate the physiological changes due to the effects of hyperthermia and 5-Fu drug individually and as a combination of both. The observed differences of cell viability losses among both cell types are measured and discussed with the expression of heat shock proteins (HSPs) by the MCF-10 cells as against the MCF-7 cancer cells. We believe that the results generated in this project can be helpful for the designing of new cancer therapeutic models with nominal adverse effects on healthy normal cells and thus paving a way for the treatment of cancer and other deadly diseases in a sustainable manner.

Development of Positively Charged Poly-L-Lysine Magnetic Nanoparticles as Potential MRI Contrast Agent.

A colloidal solution of magnetic nanoparticles (MNPs) modified with biocompatible positively charged poly-L-lysine (PLL) with an oleate (OL) layer employed as an initial coating was produced as a potential MRI contrast agent. The effect of various PLL/MNPs' mass ratios on the samples' hydrodynamic diameter, zeta potential, and isoelectric point (IEP) was studied by the dynamic light-scattering method. The optimal mass ratio for MNPs' surface coating was 0.5 (sample PLL0.5-OL-MNPs). The average hydrodynamic particle size in the sample of PLL0.5-OL-MNPs was 124.4 ± 1.4 nm, and in the PLL-unmodified nanoparticles, it was 60.9 ± 0.2 nm, indicating that the OL-MNPs' surface became covered by PLL. Next, the typical characteristics of the superparamagnetic behavior were observed in all samples. In addition, the decrease in saturation magnetizations from 66.9 Am2/kg for MNPs to 35.9 and 31.6 Am2/kg for sample OL-MNPs and PLL0.5-OL-MNPs also confirmed successful PLL adsorption. Moreover, we show that both OL-MNPs and PLL0.5-OL-MNPs exhibit excellent MRI relaxivity properties and a very high r2(*)/r1 ratio, which is very desirable in biomedical applications with required MRI contrast enhancement. The PLL coating itself appears to be the crucial factor in enhancing the relaxivity of MNPs in MRI relaxometry.

Bionic Structure Inspired by Tree Frogs to Enhance Damping Performance.

Magnetic fluid shock absorbers (MFSAs) have been successfully utilized to eliminate microvibrations of flexible spacecraft structures. The method of enhancing the damping efficiency of MFSAs has always been a critical issue. To address this, we drew inspiration from the tree frog's toe pads, which exhibit strong friction due to their unique surface structure. Using 3D printing, we integrated bionic textures copied from tree frog's toe pad surfaces onto MFSAs, which is the first time to combine bionic design and MFSAs. Additionally, this is also the first time that surface textures have been applied to MFSAs. However, we also had to consider practical engineering applications and manufacturing convenience, so we modified the shape of bionic textures. To do so, we used an edge extraction algorithm for image processing and obtained recognition results. After thorough consideration, we chose hexagon as the shape of surface textures instead of bionic textures. For theoretical analysis, a magnetic field-flow field coupling dynamic model for MFSAs was built for the first time to simulate the magnetic fluid (MF) flow in one oscillation cycle. Using this model, the flow rate contours of the MF were obtained. It was observed that textures cause vortexes to form in the MF layer, which produced an additional velocity field. This increased the shear rate, ultimately leading to an increase in flow resistance. Finally, we conducted vibration reduction experiments and estimated damping characteristics of the proposed MFSAs to prove the effectiveness of both bionic texture and hexagon surface textures. Fortunately, we concluded that hexagon surface textures not only improve the damping efficiency of MFSAs but also require less MF mass.

Research Progress on Magneto-Refractive Magnetic Field Fiber Sensors.

The magnetic field is a vital physical quantity in nature that is closely related to human production life. Magnetic field sensors (namely magnetometers) have significant application value in scientific research, engineering applications, industrial productions, and so forth. Accompanied by the continuous development of magnetic materials and fiber-sensing technology, fiber sensors based on the Magneto-Refractive Effect (MRE) not only take advantage in compact structure, superior performance, and strong environmental adaptability but also further meet the requirement of the quasi-distributed/distributed magnetic field sensing; they manifest potential and great application value in space detection, marine environmental monitoring, etc. Consequently, the present and prevalent Magneto-Refractive Magnetic Field Fiber Sensors (MR-MFSs) are briefly summarized by this paper, proceeding from the perspective of physicochemical properties; design methods, basic performance and properties are introduced systematically as well. Furthermore, this paper also summarizes key fabrication techniques and future development trends of MR-MFSs, expecting to provide ideas and technical references for staff engaging in relevant research.

Neurosurgical Applications of Magnetic Hyperthermia Therapy.

Magnetic hyperthermia therapy (MHT) is a highly localized form of hyperthermia therapy (HT) that has been effective in treating various forms of cancer. Many clinical and preclinical studies have applied MHT to treat aggressive forms of brain cancer and assessed its role as a potential adjuvant to current therapies. Initial results show that MHT has a strong antitumor effect in animal studies and a positive association with overall survival in human glioma patients. Although MHT is a promising therapy with the potential to be incorporated into the future treatment of brain cancer, significant advancement of current MHT technology is required.

Calculation of the Maximum Temperature of Diester-Based Magnetic Fluid Layers in High-Speed Seals.

Magnetic fluids, as smart nanomaterials, have been successfully used in sealing applications and other fields. However, the temperature of magnetic fluids in the sealing gap is a key factor affecting sealing performances, limiting their application in high-speed sealing fields. Since obtaining a direct measurement of the magnetic fluid's temperature is difficult, due to the small clearance, accurately calculating the maximum temperature of the magnetic fluid layer in high-speed seals is crucial. Herein, a mathematical model for calculating the maximum temperature of the magnetic fluid layer was established, by using a reasonable simplification of high-speed sealing conditions, and the calculation formula was modified by studying the rheological properties of the diester-based magnetic fluid. The results suggest that the calculation of the maximum temperature is influenced by viscous dissipation, and both are related to the rheological characteristics of magnetic fluids. When the influence of rheological properties is ignored, the calculation results are not accurate for higher-velocity seals, but the calculation model applies to lower-velocity seals. When the influence of rheological properties is considered, the calculation results obtained by the corrected formula are more accurate, and they are applicable to both lower- and higher-velocity seals. This work can help us more accurately and conveniently estimate the maximum temperature of magnetic fluids in high-speed seal applications, which is of theoretical and practical research significance for determining sealing performances and thermal designs.

Magnetorheological and Viscoelastic Behaviors in an Fe-Based Amorphous Magnetic Fluid.

A novel magnetic fluid was obtained using a colloidal dispersion of amorphous magnetic Fe-Ni-B nanoparticles into water. Its magnetorheological and viscoelastic behaviors were all investigated. Results showed that the generated particles were spherical amorphous particles 12-15 nm in diameter. The saturation magnetization of Fe-based amorphous magnetic particles could reach 49.3 emu/g. The amorphous magnetic fluid exhibited shear shinning behavior under magnetic fields and showed strong magnetic responsiveness. The yield stress increased with the rising magnetic field strength. A crossover phenomenon was observed from the modulus strain curves due to the phase transition under applied magnetic fields. The storage modulus G' was higher than the loss modulus G″ at low strains, while G' was lower than G″ at high strains. The crossover points shifted to higher strains with increasing magnetic field. Furthermore, G' decreased and fell off in a power law relationship when the strain exceeded a critical value. However, G″ showed a distinct maximum at a critical strain, and then decreased in a power law fashion. The magnetorheological and viscoelastic behaviors were found to be related to the structural formation and destruction in the magnetic fluids, which is a joint effect of magnetic fields and shear flows.

Proton Therapy, Magnetic Nanoparticles and Hyperthermia as Combined Treatment for Pancreatic BxPC3 Tumor Cells.

We present an investigation of the effects on BxPC3 pancreatic cancer cells of proton therapy combined with hyperthermia, assisted by magnetic fluid hyperthermia performed with the use of magnetic nanoparticles. The cells' response to the combined treatment has been evaluated by means of the clonogenic survival assay and the estimation of DNA Double Strand Breaks (DSBs). The Reactive Oxygen Species (ROS) production, the tumor cell invasion and the cell cycle variations have also been studied. The experimental results have shown that the combination of proton therapy, MNPs administration and hyperthermia gives a clonogenic survival that is much smaller than the single irradiation treatment at all doses, thus suggesting a new effective combined therapy for the pancreatic tumor. Importantly, the effect of the therapies used here is synergistic. Moreover, after proton irradiation, the hyperthermia treatment was able to increase the number of DSBs, even though just at 6 h after the treatment. Noticeably, the magnetic nanoparticles' presence induces radiosensitization effects, and hyperthermia increases the production of ROS, which contributes to cytotoxic cellular effects and to a wide variety of lesions including DNA damage. The present study indicates a new way for clinical translation of combined therapies, also in the vision of an increasing number of hospitals that will use the proton therapy technique in the near future for different kinds of radio-resistant cancers.