Hyperthermia Cancer Therapy Research Articles

Combination of magnetic hyperthermia and gene therapy for breast cancer.

This study presented a novel breast cancer therapy model that uses magnetic field-controlled heating to trigger gene expression in cancer cells. We created silica- and amine-modified superparamagnetic nanoparticles (MSNP-NH2) to carry genes and release heat under an alternating current (AC) magnetic field. The heat-inducible expression plasmid(pHSP-Azu) was designed to encode anti-cancer azurin and was delivered by magnetofection. MCF-7 cells demonstrated over 93% cell viability and 12% transfection efficiency when exposed to 75µg/ml of MSNP-NH2, 3µg of DNA, and PEI at a 0.75 PEI/DNA ratio (w: w), unlike non-tumorigenic cells (MCF-10A). Magnetic hyperthermia (MHT) increased azurin expression by heat induction, leading to cell death in dual ways. The combination of MHT and heat-regulated azurin expression induced cell death, specifically in cancer cells, while having negligible effects on MCF-10A cells. The proposed strategy clearly shows that simultaneous use of MHT and MHT-induced azurin gene expression may selectively target and kill cancer cells, offering a promising direction for cancer therapy.

Temporal Optimization in the Synthesis of Multifunctional Nano Agents for Enhanced MRI Contrast, Hyperthermia Therapy, and ROS Generation.

Advanced methodologies, such as hyperthermia and modulation of reactive oxygen species (ROS), exhibit considerable promise in the therapeutic landscape of cancer. These strategies offer a targeted paradigm for combating malignant cells while mitigating damage to healthy tissue. Noteworthy among these approaches is the utilization of superparamagnetic iron oxide nanoparticles, which are renowned for their ability to enhance both hyperthermia and ROS generation specifically within tumor microenvironments. The objective of this investigation is to scrutinize the relationship between the reaction duration and the characteristics of carbon-doped silica core-shell iron oxide nanoparticles (CSIONPs). Specifically, we focus on CSIONP-12, CSIONP-24, and CSIONP-36, synthesized by using varying reaction periods. Through a comprehensive analysis, we primarily evaluate the impact of these formulations on T1 and T2 magnetic resonance imaging (MRI), aiming to elucidate their mechanisms and therapeutic potential in promoting hyperthermia and ROS-mediated cancer therapy. CSIONP-24 emerges as a compelling candidate due to its dual influence on magnetic hyperthermia and ROS generation, suggesting its promise in enhancing cancer treatment outcomes. Furthermore, the findings underscore the exceptional T1-T2 MRI capabilities of this technology, underscoring its versatility and efficacy in the nuanced realm of cancer theranostic.

Magnetic hyperthermia in cancer therapy, mechanisms, and recent advances: A review.

Hyperthermia therapy refers to the elevating of a region in the body for therapeutic purposes. Different techniques have been applied for hyperthermia therapy including laser, microwave, radiofrequency, ultrasonic, and magnetic nanoparticles and the latter have received great attention in recent years. Magnetic hyperthermia in cancer therapy aims to increase the temperature of the body tissue by locally delivering heat from the magnetic nanoparticles to cancer cells with the aid of an external alternating magnetic field to kill the cancerous cells or prevent their further growth. This review introduces magnetic hyperthermia with magnetic nanoparticles. It includes the mechanism of the operation and magnetism behind the magnetic hyperthermia phenomenon. Different synthesis methods and surface modification to enhance the biocompatibility, water solubility, and stability of the nanoparticles in physiological environments have been discussed. Recent research on versatile types of magnetic nanoparticles with their ability to increase the local temperature has been addressed.

A novel ternary magnetic nanobiocomposite based on tragacanth-silk fibroin hydrogel for hyperthermia and biological properties.

This study involves the development of a new nanocomposite material for use in biological applications. The nanocomposite was based on tragacanth hydrogel (TG), which was formed through cross-linking of Ca2+ ions with TG polymer chains. The utilization of TG hydrogel and silk fibroin as natural compounds has enhanced the biocompatibility, biodegradability, adhesion, and cell growth properties of the nanobiocomposite. This advancement makes the nanobiocomposite suitable for various biological applications, including drug delivery, wound healing, and tissue engineering. Additionally, Fe3O4 magnetic nanoparticles were synthesized in situ within the nanocomposite to enhance its hyperthermia efficiency. The presence of hydrophilic groups in all components of the nanobiocomposite allowed for good dispersion in water, which is an important factor in increasing the effectiveness of hyperthermia cancer therapy. Hemolysis and 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were conducted to evaluate the safety and efficacy of the nanobiocomposite for in-vivo applications. Results showed that even at high concentrations, the nanobiocomposite had minimal hemolytic effects. Finally, the hyperthermia application of the hybrid scaffold was evaluated, with a maximum SAR value of 41.2W/g measured in the first interval.

An extended model to assess Jeffery–Hamel blood flow through arteries with iron-oxide (Fe2O3) nanoparticles and melting effects: Entropy optimization analysis

Abstract Nanofluids are utilized in cancer therapy to boost therapeutic effectiveness and prevent adverse reactions. These nanoparticles are delivered to the cancerous tissues under the influence of radiation through the blood vessels. In the current study, the propagation of nanoparticles within the blood in a divergent/convergent vertical channel with flexible boundaries is elaborated computationally. The base fluid (Carreau fluid model) is speculated to be blood, whereas nanofluid is believed to be an iron oxide–blood mixture. Because of its shear thinning or shear thickening features, the Carreau fluid model more precisely depicts the rheological characteristics of blood. The arterial section is considered a convergent or divergent channel based on its topological configuration (non-uniform cross section). An iron oxide ( F e 2 O 3 {\rm{F}}{{\rm{e}}}_{2}{{\rm{O}}}_{3} ) nanoparticle is injected into the blood (base fluid). To eliminate the viscous effect in the region of the artery wall, a slip boundary condition is applied. An analysis of the transport phenomena is preferred using the melting heat transfer phenomena, which can work in melting plaques or fats at the vessel walls. The effects of thermal radiation, which is advantageous in cancer therapy, biomedical imaging, hyperthermia, and tumor therapy, are incorporated in heat transport mechanisms. The governing equation for the flow model with realistic boundary conditions is numerically tickled using the RK45 mechanism. The findings reveal that the flow dynamism and thermal behavior are significantly influenced by melting effects. Higher Re \mathrm{Re} can produce spots in which the track of the wall shear stress fluctuates. The melting effects can produce agitation and increase the flow through viscous head losses, causing melting of the blockage. The maximum heat transfer of 5 % 5 \% is achieved with We {\rm{We}} when the volume friction is kept at 1 % 1 \% . With higher estimation of inertial forces Re \mathrm{Re}\hspace{1em} and same volume friction, the skin drag coefficient augmented to 34 % 34 \% . The overall temperature is greater for the divergent flow scenario.

Dual Functional Magnetic Nanoparticles Conjugated with Carbon Quantum Dots for Hyperthermia and Photodynamic Therapy for Cancer.

The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.

Dumbbell-like Au–Fe3O4 nanoparticles for magnetic hyperthermia

Dumbbell-shaped hybrid nanoparticles, consisting of gold and iron oxide (Au-Fe3O4 NPs), show promise for magnetic hyperthermia cancer therapy. However, conventional synthesis methods using toxic iron pentacarbonyl (Fe(CO)5) raise safety concerns. We propose a safer approach using triiron dodecacarbonyl (Fe3(CO)12) as a precursor. We synthesize these NPs by initially reducing gold (III) chloride trihydrate with a tert-butylamine-borane complex at room temperature, yielding Au NPs. These Au NPs are combined with a Fe3(CO)12 solution and heated to 300 °C for 1 hour, resulting in the desired dumbbell-shaped Au-Fe3O4 NPs. Characterization confirms their morphology, with average sizes of 5 nm for Au NPs and 15 nm for Fe3O4 NPs. Our systematic evaluation of hydrophilic-treated Au-Fe3O4 NPs (Ms=49.5 emu/g at 3T, 300K) demonstrates temperature increases beyond the therapeutic threshold of 45 °C (ΔT=8 °C) at higher field strengths (8.6–30.0 kA/m), highlighting their cancer treatment potential. Quantitative analysis reveals superb performance, with a specific absorption rate (SAR) of 60.0 W/g and intrinsic loss power (ILP) of 0.25 nHm2kg−1 at the maximum field strength. These findings emphasize the significant potential of our dumbbell-shaped Au–Fe3O4 NPs for magnetic hyperthermia.

Safety evaluation of PEGylated MNPs and p-PEGylated MNPs in SD rats

Polyethylene glycol-coated magnetic nanoparticles (PEGylated MNPs) have demonstrated prominent advantages in cancer diagnosis and hyperthermia therapy. However, there is currently lack of standard mode and sufficient toxicity data for determining the delayed risk of PEGylated MNPs. Nevertheless, the toxicity potentials, especially those associated with the oxidative stress, were ubiquitously reported. In this study, PEGylated MNPs and p-PEGylated MNPs were administrated to SD (Sprague Dawley) rats by single intravenously injection, and various toxicity indicators were monitored till 56 days post-administration for a comprehensive toxicity evaluation. We revealed that both nanoparticles could be rapidly cleared from plasma and enter tissues, such as, liver, kidneys and spleen, and p-PEGylated MNP is less prone to be accumulated in the tissues, indicating a lower toxicity risk. PEGylated MNPs were more likely to up-regulate the expression levels of Th2 type cytokines and trigger inflammatory pathways, but no related pathological change was found. Both MNPs are not mutagenic, while recoverable mild DNA damage associated with the presence of nanoparticles might also be observed. This study demonstrated a research approach for the non-clinical safety evaluation of nanoparticles. It also provided comprehensive valuable safety data for PEGylated and p-PEGylated MNPs, for promoting the clinical application and bio-medical translation of such MNPs with PEG modifications in the cancer diagnosis and therapy.

Accelerator production, radiochemical separation and nanoradiopharmaceutical formulation using 69Ge: A next generation PET probe

Positron emission tomography (PET) has revolutionized the field of molecular imaging of cancer. The driving forces in the latest resurgence of PET are the advances in nano-oncology and availability of newer radioisotopes with attractive nuclear decay characteristics. Germanium-69 (69Ge; T½ = 39 h, 21 % β+, Emax = 1205 keV) is one such radioisotope whose potential is yet to be fully explored for PET imaging. The adequately long half-life of 69Ge, makes it an ideal choice for PET imaging using radiolabeled nanoformulations, which are expected to circulate for a relatively longer time in the biological system. In this study, we report the production of 69Ge via 69Ga (p, n) 69Ge reaction using natural Ga2O3 target. A facile radiochemical separation method based on selective precipitation of Ga at pH ∼7 was developed for isolating no-carrier-added (NCA) 69Ge from the irradiated target in a form suitable for in vivo animal studies. A chelator-free approach was optimized for radiolabeling superparamagnetic arginine grafted iron oxide nanoparticles (AMNPs) with 69Ge for potential use in dual modality PET/magnetic resonance imaging (MRI) and magnetic hyperthermia therapy of cancer. The radiolabeling yield of 69Ge-AMNPs was >95 % and the radiolabeled nanoformulation was stable even after 72 h. As a proof of concept, the suitability of the radiolabeled nanoformulation for in vivo PET imaging was demonstrated in Wistar rats. Overall, this strategy of production, radiochemical separation and radiopharmaceutical formulation might aid towards development of potent agents for cancer theranostics.

2D Nanomaterials and Their Drug Conjugates for Phototherapy and Magnetic Hyperthermia Therapy of Cancer and Infections.

Photothermal therapy (PTT) and magnetic hyperthermia therapy (MHT) using 2D nanomaterials (2DnMat) have recently emerged as promising alternative treatments for cancer and bacterial infections, both important global health challenges. The present review intends to provide not only a comprehensive overview, but also an integrative approach of the state-of-the-art knowledge on 2DnMat for PTT and MHT of cancer and infections. High surface area, high extinction coefficient in near-infra-red (NIR) region, responsiveness to external stimuli like magnetic fields, and the endless possibilities of surface functionalization, make 2DnMat ideal platforms for PTT and MHT. Most of these materials are biocompatible with mammalian cells, presenting some cytotoxicity against bacteria. However, each material must be comprehensively characterized physiochemically and biologically, since small variations can have significant biological impact. Highly efficient and selective in vitro and in vivo PTTs for the treatment of cancer and infections are reported, using a wide range of 2DnMat concentrations and incubation times. MHT is described to be more effective against bacterial infections than against cancer therapy. Despite the promising results attained, some challenges remain, such as improving 2DnMat conjugation with drugs, understanding their in vivo biodegradation, and refining the evaluation criteria to measure PTT or MHT effects.

(Magnetite/poly(ε-caprolactone))/chitosan (core/shell)/shell nanocomposites with potential applications in hyperthermia cancer therapy

Magnetic (core/shell)/shell nanoparticles are promising tools for biomedical applications based on hyperthermia. In this work, magnetite particles were obtained by chemical coprecipitation and were used in the preparation of a (magnetite/poly(ε-caprolactone)/chitosan nanocomposite. That (core/shell)/shell nanostructure was characterized by electron microscopy, energy-dispersive X-ray spectroscopy, electrophoresis, thermogravimetric analysis, and X-ray diffraction spectroscopy. The effect on the heating efficiency of the nanocomposite at different magnetic field strengths were investigated finding that, even at low field strengths, the hyperthermia range was reached rapidly. Negligible toxicity of the particles was postulated given their null effect on blood components. These magneto-polymer composite particles could find a promising application in antitumor magnetic hyperthermia.

Magnetic hyperthermia cancer therapy using rare earth metal-based nanoparticles: An investigation of Lanthanum strontium Manganite's hyperthermic properties

Magnetic hyperthermia cancer therapy has emerged as a promising approach for targeted and localized treatment of cancer. This innovative technique utilizes magnetic nanoparticles to generate localized heat within tumor cells, leading to their selective destruction. This study explores the hyperthermic potential of Lanthanum Strontium Manganite (LSMO), which are rare earth metal-based magnetic nanoparticles, for their application in magnetic hyperthermia cancer therapy. A modified citrate sol-gel technique was utilized to create LSMO (La0·7Sr0·3MnO3) nanoparticles, which were then modified by coating with silica. Comprehensive physical characterization of the nanoparticles was performed, and their hyperthermic potential was evaluated in vitro. The biocompatibility and selective cytotoxicity of LSMO nanoparticles were investigated, and the results demonstrated promising outcomes. With its controlled and localized heat generation and enhanced biocompatibility, LSMO offers an encouraging avenue for advancing targeted and effective cancer treatments. Future research in this field may pave the way for transformative improvements in cancer therapy outcomes.

Nanoengineering Liquid Metal Core–Shell Nanostructures

AbstractNanoengineering the composition and morphology of functional nanoparticles endows them to perform multiple tasks and functions. An intriguing strategy for creating multifunctional nanomaterials involves the construction of core–shell nanostructures, which have enabled promising applications in biomedicine, energy, sensing, and catalysis. Here, a straightforward nanoengineering approach is presented utilizing liquid metal nanoparticles and galvanic replacement to create diverse core–shell nanostructures. Controlled nanostructures including liquid metal core‐gold nanoparticle shell (LM@Au), gold nanoparticle core‐gallium oxide shell (Au@Ga oxide), and hollow Ga oxide nanoparticles are successfully fabricated. Remarkably, these investigations reveal that LM@Au exhibits exceptional photothermal performance, achieving an impressive conversion efficiency of 65.9%, which is five times that of gold nanoparticles. By leveraging the high photothermal conversion efficiency and excellent biocompatibility of LM@Au, its promising application in hyperthermia cancer therapy is demonstrated. This simple yet powerful nanoengineering strategy opens new avenues for the controlled synthesis of complex core–shell nanostructures, advancing various fields beyond biomedicine.

Chitosan decorated cobalt zinc ferrite nanoferrofluid composites for potential cancer hyperthermia therapy: anti-cancer activity, genotoxicity, and immunotoxicity evaluation

Cancer, as the leading cause of death worldwide, has been constantly increasing in mortality every year. Among several therapeutics, nanoscale compounds showed promising results in overcoming cancer diseases. There are numerous types of research on the paramagnetic nanoparticles of iron oxide, which cause apoptosis and cancer cell death. In this study, cobalt/zinc/ferrite nanoferrofluid composites (~ 39 nm) were synthesized and decorated with chitosan to enhance the cell entry for potential applications in cancer therapy. The neat and chitosan-adorned cobalt zinc ferrite nanoferrofluid composites (~ 94 nm) displayed superparamagnetic properties. The nanocomposite exhibited anti-cancer activity against WEHI164 cancer cells in a dose- and time-dependent manner. The chitosan-coated nanocomposite was found to induce oxidative stress in WEHI164 cancer cells, as indicated by reactive oxygen species (ROS) production. Furthermore, DNA damage was indicated in WEHI164 cancer cells after exposure to chitosan-coated nanocomposites. Chitosan-coated nanocomposites promoted dendritic cell maturation by inducing the release of interleukin-6 proinflammatory cytokines. According to the results and ancillary studies, superparamagnetic nanoparticles coated with chitosan can be considered an effective and promising treatment for the destruction of cancer cells. Graphical Summary: Chitosan decorated cobalt zinc ferrite nanoferrofluid composites was fabricated for potential cancer hyperthermia therapy with high biocompatibility.

Enhancing Gastric Cancer Therapeutic Efficacy through Synergistic Cotreatment of Linderae Radix and Hyperthermia in AGS Cells.

Gastric cancer remains a global health threat, particularly in Asian countries. Current treatment methods include surgery, chemotherapy, and radiation therapy. However, they all have limitations, such as adverse side effects, tumor resistance, and patient tolerance. Hyperthermia therapy uses heat to selectively target and destroy cancer cells, but it has limited efficacy when used alone. Linderae Radix (LR), a natural compound with thermogenic effects, has the potential to enhance the therapeutic efficacy of hyperthermia treatment. In this study, we investigated the synergistic anticancer effects of cotreatment with LR and 43 °C hyperthermia in AGS gastric cancer cells. The cotreatment inhibited AGS cell proliferation, induced apoptosis, caused cell cycle arrest, suppressed heat-induced heat shock responses, increased reactive oxygen species (ROS) generation, and promoted mitogen-activated protein kinase phosphorylation. N-acetylcysteine pretreatment abolished the apoptotic effect of LR and hyperthermia cotreatment, indicating the crucial role of ROS in mediating the observed anticancer effects. These findings highlight the potential of LR as an adjuvant to hyperthermia therapy for gastric cancer. Further research is needed to validate these findings in vivo, explore the underlying molecular pathways, and optimize treatment protocols for the development of novel and effective therapeutic strategies for patients with gastric cancer.

Engineering Near‐Infrared Plasmonic Spiky Gold Nanostructures for Highly Efficient Surface‐Enhanced Raman Spectroscopy‐Guided Cancer Hyperthermia Therapy

AbstractCancer phototheranostics utilizing plasmonic materials is attracting considerable interest due to its high spatiotemporal precision and specificity, remote controllability, superior therapeutic efficacy, and low systemic side effects. Exploring new plasmonic materials with excellent plasmonic and photothermal properties is at the frontier of cancer phototheranostics. Herein, this work systematically investigates the plasmonic and photothermal properties of spiky Au nanoparticles (NPs) with different shaped central cores – spiky Au nanosphere , spiky Au nanocube and spiky Au nanorod (AuNR). It is shown that the shape of the central core in spiky Au NPs has significant effects on their surface‐enhanced Raman spectroscopy (SERS) and photothermal performances, and spiky Au NPs of a spherical or cubic core are much superior for near‐infrared (NIR) SERS detection and hyperthermia therapy in comparison with spiky AuNRs. The spiky Au NP‐based SERS probes demonstrate the remarkable capability for SERS imaging of live cells and dynamic visualization of tumors in a 4T1 breast tumor mouse model after intravenous administration. Moreover, in vivo studies show exceptional hyperthermia therapeutic effects of such SERS probes against 4T1 breast tumors under NIR irradiation. This study suggests the potential utility of spiky Au NP‐based SERS probes for efficient SERS‐guided cancer hyperthermia therapy.

Oxygen vacancy enhanced magnetic heating efficiency of ferrite nanoparticles for self-regulating temperature hyperthermia

Precise and controllable temperature is required for using magnetic hyperthermia in cancer therapy. Magnetic nanoparticles typically need to have a Curie temperature of 42–50 °C to self-regulate hyperthermia temperature via magnetic phase transition. For now, the most studied iron oxide nanoparticles are not suitable for self-regulating hyperthermia applications due to their high Curie temperature of several hundred Celsius degrees. Doping nonmagnetic metal ions into iron oxide nanoparticles is an effective way to decrease Curie temperature, but often leads to low saturation magnetization and poor magnetic heating efficiency, limiting its usage in hyperthermia applications. Magnetic nanoparticles with excellent magnetic heating efficiency and suitable Curie temperature are highly desirable. This paper proposes an approach for enhancing magnetic heating efficiency by regulating oxygen vacancy concentration. Mn0.46Zn0.54Al0.25Fe1.75O4 nanoparticles with Curie temperature at 44.5 °C are prepared by co-precipitation method. Effective regulation of oxygen vacancy concentrations is achieved through hydrogen peroxide oxidation and carbothermal reduction treatments. Research results suggest that increasing oxygen vacancies significantly enhance the magnetism due to the transformation of magnetic couplings on nanoparticles, while barely affecting the Curie temperature. These nanoparticles exhibit high magnetic heating efficiency under an alternating magnetic field, almost 1.5 times of clinical-grade iron oxide nanoparticles, and can self-regulate hyperthermia temperature at 48–49 °C. This work may provide some references for further research on self-regulating temperature magnetic hyperthermia.

High temperature flow synthesis of iron oxide nanoparticles: Size tuning via reactor engineering

Batch thermal decomposition syntheses of iron oxide nanoparticles (IONPs) provide precise control of particle properties, but their scalability and reproducibility is challenging. This is addressed in this work via a versatile high temperature flow reactor with adjustable temperature profiles through three individual stages operated between 180 °C and 280 °C. The tuneable temperature profiles in combination with self-seeded growth methods made it possible to synthesise IONPs between 2 and 17 nm (a size increase that corresponds to a >600 fold particle volume increase) at production rates of several gIONP per day. The precursor solutions contained only iron(III) acetylacetonate in a polyol solvent and no nucleation or growth inhibitors, oxidation or reducing agents, ligands or any other additives . This broad size range covers most biomedical applications and is of special interest for T1 MRI contrast agents (2–5 nm), as well as for magnetic hyperthermia cancer therapy (>10 nm). The potential of the IONPs produced was demonstrated by their high longitudinal relaxivity >16 mM−1s−1 at a transversal/longitudinal relaxivity ratio <2.5 (small IONPs) and specific absorption rates increasing with the IONP size up to180 W/gFe. In addition, the polyol method employed allowed for simple ligand exchange with biocompatible sodium tripolyphosphate to make the IONPs stable in water, thus rendering them suitable for biomedical applications. The continuous high temperature process presented shows how to control the particle size not via the chemistry (e.g., chemical additives affecting the particle size through the surface chemistry), but engineering parameters, i.e., reactor temperature profiles, reagent addition sequences and seeded growth strategies.

Synthesis of carbon nano-onions filled with γ-Fe and Gd/GdCl3: A candidate multifunctional system

Stabilization of high-spin high-volume ferromagnetic γ-Fe nanocrystals inside carbon nano-onions (CNOs) has recently attracted an important attention for possible applications in magnetic hyperthermia cancer therapy. Here we report an advanced investigation of the chemical vapour synthesis (CVS) fabrication methodology of the filled CNOs, with focus on 1) the stabilization of the γ-Fe nanocrystals in presence of larger concentration of Cl radicals and 2) the structural functionalization, through simultaneous encapsulation of both ferromagnetic γ-Fe and paramagnetic GdCl3 phases. By employing HRTEM we demonstrate an anomalous structural configuration of the CNOs, involving the coexistence of defect-rich concentrical-like and radially-oriented graphitic layers. XPS and Raman spectroscopy evidence the presence of CS bond-formation and defect nucleation as key parameters for the growth of the radially-oriented graphitic layers. This unusual structural arrangement of the CNO is found to stabilize the γ-Fe phase at room temperature. We highlight the absence of FCC to BCC structural relaxation within timescales of 8 months from sample-fabrication. XRD, Rietveld refinements, together with magnetometry confirm the presence of a ferromagnetic transition arising below T ∼ 70 K within γ-Fe. This interpretation is further corroborated through extended characterization with ESR spectroscopy. Structural manipulation and functionalization of the CNOs is demonstrated by including tris(tetramethyl-cyclopentadienyl)gadolinium(III) as a precursor in the pyrolysis experiments. The functionalized CNO (filled with ferromagnetic γ-Fe/Fe3C and paramagnetic Gd/GdCl3) can be visualized as a multifunctional-container and a candidate for magnetic-hyperthermia-cancer-therapy and MRI contrast applications.

Distinct effects of heat shock temperatures on mitotic progression by influencing the spindle assembly checkpoint

Heat shock is a physiological and environmental stress that leads to the denaturation and inactivation of cellular proteins and is used in hyperthermia cancer therapy. Previously, we revealed that mild heat shock (42 °C) delays the mitotic progression by activating the spindle assembly checkpoint (SAC). However, it is unclear whether SAC activation is maintained at higher temperatures than 42 °C. Here, we demonstrated that a high temperature of 44 °C just before mitotic entry led to a prolonged mitotic delay in the early phase, which was shortened by the SAC inhibitor, AZ3146, indicating SAC activation. Interestingly, mitotic slippage was observed at 44 °C after a prolonged delay but not at 42 °C heat shock. Furthermore, the multinuclear cells were generated by mitotic slippage in 44 °C-treated cells. Immunofluorescence analysis revealed that heat shock at 44 °C reduces the kinetochore localization of MAD2, which is essential for mitotic checkpoint activation, in nocodazole-arrested mitotic cells. These results indicate that 44 °C heat shock causes SAC inactivation even after full activation of SAC and suggest that decreased localization of MAD2 at the kinetochore is involved in heat shock-induced mitotic slippage, resulting in multinucleation. Since mitotic slippage causes drug resistance and chromosomal instability, we propose that there may be a risk of cancer malignancy when the cells are exposed to high temperatures.