In recent years, porous bifunctional scaffolds with hyperthermal and tissue regeneration functions play an essential role in the efficient cancerous bone tumors treatment. In this work, the nanocomposite scaffolds of gelatin (polymer phase) and akermanite (ceramic phase) were prepared by entrapping carboxyl-functionalized multi-walled carbon nanotube (MWNT) and embedding magnetic nanoparticles of iron oxide into the porous matrix as photothermal conversion agents. The obtained scaffolds and their components were characterized using FTIR, FESEM, TEM, EDS, DLS, and VSM analysis. The mechanical properties of the prepared scaffolds were also investigated. The swelling behavior of the scaffolds in PBS as well as biodegradation and protein adsorption capability were evaluated. The addition of nanoparticles into the gelatin/akermanite matrix efficiently increased the adsorption of bovine serum albumin on the surface of the composite scaffold and contrarily decreased its degradation rate in the presence of lysozyme. The prepared scaffolds exhibited a high photothermal performance using NIR laser with different power intensity and irradiation time. Finally, the biocompatibility of the scaffold was confirmed using G292 osteoblastic cells through MTT assays. It can therefore be concluded that synthesized scaffolds have a great potential in bone tissue engineering and probably treatment of tumor related bone defects.

Heat generation by pointlike structures is an appealing concept for its implications in nanotechnology and biomedicine. The way to pump energy that excites heat locally and the synthesis of nanostructures that absorb such energy are key issues in this endeavor. High-frequency alternating magnetic or near-infrared optical fields are used to induce heat in iron oxide nanoparticles, a combined solution that is being exploited in hyperthermia treatments. However, the temperature determination around a single iron oxide nanoparticle remains a challenge. We study the heat released from iron oxide nanostructures under near-infrared illumination on a one-by-one basis by optical tweezers. To measure the temperature, we follow the medium viscosity changes around the trapped particle as a function of the illuminating power, thus avoiding the use of thermal probes. Our results help interpret temperature, a statistical parameter, in the nanoscale and the concept of heat production by nanoparticles under thermal agitation.

The efficiency of ultrasound hyperthermia for anti-cancer treatments such as radiotherapy or chemotherapy can be improved by using sonosensitizers, which are materials that enhance the attenuation and dissipation of acoustic energy. We propose the use of magnetic nanoparticles as sonosensitizers because of their biocompatibility, nontoxicity, and common use in several medical applications. A magnetic material was synthetized and then incorporated in the form of a magnetic fluid in agar tissue-mimicking phantoms. Ultrasound hyperthermia studies were conducted at various ultrasound frequencies and concentrations of magnetic nanoparticles in the phantoms. The theoretical modeling based on a heat transfer equation and the experimental results show good agreement and confirm that the temperature rise during ultrasound heating in tissue-mimicking phantoms doped with sonosensitizers is greater than that in a pure agar phantom. Furthermore, on the basis of Pennes' bio-heat equation, which takes into consideration the blood perfusion and metabolic heat, the thermal dose and lesion shapes after sonication were determined for a hypothetical tissue.

In this work, near-infrared fluorescence (NIRF) and magnetic resonance (MR) dual-modality imaging probes are prepared by conjugating maleimide derivative cyanine dye (Mal-Cy5.5), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), and RGD peptide (Mal-PEG2-RGD) on thioether-bridged mesoporous organosilica nanoparticles (MONs) via click reaction. Fourier transform infrared (FT-IR) spectra, zeta potentials, UV-vis spectra, and energy dispersive X-ray (EDX) spectrum confirm the successful modifications of the functional molecules on the MONs. The prepared MON-Gd-Cy5.5-RGD probes shows excellent NIRF and MR imaging properties, and the relaxivity rate (r1) is measured up to 2.85 mM s . In addition, the MON-Gd-Cy5.5-RGD probes show excellent in vitro and in vivo biocompatibility. Confocal laser scanning microscopy and flow cytometry demonstrate that the MON-Gd-Cy5.5-RGD can efficiently target to MDA-MB-231 tumor cells. Additionally, ex vivo NIFR and in vivo MR imaging demonstrate that the MON-Gd-Cy5.5-RGD probes can accumulate in tumor and improve the signals of tumor.

Targeted delivery of enzyme-activatable probes into cancer cells to facilitate accurate imaging and on-demand photothermal therapy (PTT) of cancers with high spatiotemporal precision promises to advance cancer diagnosis and therapy. Here, we report a tumor-targeted and matrix metalloprotease-2 (MMP-2)-activatable nanoprobe (T-MAN) formed by covalent modification of Gd-doping CuS micellar nanoparticles with cRGD and an MMP-2-cleavable fluorescent substrate. T-MAN displays a high r relaxivity (∼60.0 mM s per Gd at 1 T) and a large near-infrared (NIR) fluorescence turn-on ratio (∼185-fold) in response to MMP-2, allowing high-spatial-resolution magnetic resonance imaging (MRI) and low-background fluorescence imaging of gastric tumors as well as lymph node (LN) metastasis in living mice. Moreover, T-MAN has a high photothermal conversion efficiency (PCE, ∼70.1%) under 808 nm laser irradiation, endowing it with the ability to efficiently generate heat to kill tumor cells. We demonstrate that T-MAN can accumulate preferentially in gastric tumors (∼23.4% ID%/g at 12 h) after intravenous injection into mice, creating opportunities for fluorescence/MR bimodal imaging-guided PTT of subcutaneous and metastatic gastric tumors. For the first time, accurate detection and laser irradiation-initiated photothermal ablation of orthotopic gastric tumors in intraoperative mice was also achieved. This study highlights the versatility of using a combination of dual biomarker recognition (i.e., αβ and MMP-2) and dual modality imaging (i.e., MRI and NIR fluorescence) to design tumor-targeting and activatable nanoprobes with improved selectivity for cancer theranostics in vivo.

In this work, we designed a new strategy for ultrasensitive detection of CEA based on efficient electrochemiluminescence (ECL) quenching of Ru(bpy)-doped SiO nanocomposite by ferrocene using target recycling amplification technique. A large number of Ru@SiO ECL signal probe were firstly assembled on the novel magnetic core-shell FeO@Au nanoparticles (NPs), then the ferrocene-labeled ECL quenching probe (Fc-probe) was linked to the magnetic NPs. Finally, numerous DNA1 sequences were produced by target CEA-triggered multiple recycling amplification and displaced the Fc-probe on the magnetic NPs, leading to significantly enhanced ECL signal for CEA detection. Because of the designed cascade signal amplification strategy, the newly developed method achieved a wide linear range of 10 fg/mL to 10 ng/mL with a low detection limit of  3.5 fg/mL. Furthermore, taking advantages of the magnetic FeO@Au NPs for carring abundant signal probes, sensing target and ECL detection, the developed ECL strategy is convenient, rapid and displayed high sensitivity for CEA detection, which has great potential for analyzing the clinical samples in practical disease diagnosis applications.

Because of their high magnetization and suitable biocompatibility, iron-oxide nanoparticles (IONPs) have been widely employed in various biomedical applications, including magnetic hyperthermia for cancer treatment. In many cases, the colloidal stability requirement will limit the usage of ferromagnetic particles that are usually associated with good magnetic response. To address this challenge, a stable carrier for better colloidal stability regardless of the size or shape of the IONPs while at the same time providing enhanced magnetic hyperthermia heating performance is required. In this work, IONPs of different sizes (4, 8, 20, 45, and 250 nm) were engineered to reside in the graphene oxide (GO) sheet carrier, which were stable in aqueous solution even in the presence of a strong magnetic field. Out of various IONPs sizes, highest specific absorption rate (SAR) value of 5020 W g was obtained with 45 nm GO-IONPs nanocomposites at a frequency and alternating magnetic field of 400 kHz and 32.5 kA m, respectively. The calculated intrinsic loss power (ILP) was 12.21 nH m kg, which is one of the highest ILP values reported for synthesized IONPs to the best of our knowledge. To enhance the excellent colloidal stability in biological environment, the GO-IONPs nanocomposites can be further grafted with polyethylene glycol (PEG) because agglomeration of pristine GO sheets occurs because of adsorption of cations. High ILP values could be well maintained even after PEG coating. The PEGylated 45 nm GO-IONP showed excellent antitumor efficacy in 4T1-tumor model mice by inhibiting tumor progression within a safe dosage range. Overall, the novel nanocomposite in this work-PEG-GO-IONP-possesses high hyperthermia performance, excellent colloidal stability in biological environment, and availability of functional groups in GO and can be utilized for tagging in various biomedical applications.

Cold atmospheric plasma (CAP) is an emerging biomedical technique that shows great potential for cancer treatment. On the other hand, magnetic nanoparticles open up a wide field of possible applications in medicine. Here we seek to develop a novel dual cancer therapeutic method by integrating promising CAP and iron oxide-based magnetic nanoparticles (MNPs), and evaluate its underlying mechanism for targeted lung cancer treatment. For this purpose, the synergistic effects of CAP and iron oxide-based MNPs on cellular bioactivity, epidermal growth factor receptor (EGFR) expression, and EGFR downstream signaling pathways were investigated. Results showed that the effectiveness of CAP and iron oxide-based MNPs for synergistic strongly killed activity against lung cancer cells, and significantly inhibited cell proliferation via reduction of viability and induction of apoptosis. Importantly, CAP combining with iron oxide-based MNPs induced EGFR downregulation while CAP inhibited lung cancer cells via depressing pERK and pAKT. Translation of these findings to an in vivo setting demonstrates that CAP combining iron oxide-based MNPs is effective at preventing xenograft tumors. Thus, the integration of CAP and iron oxide-based MNPs provides a promising tool for the development of a new cancer treatment strategy.

In the past decade, iron oxide nanoparticles (IONPs) have attracted more and more attention for their excellent physicochemical properties and promising biomedical applications. In this review, we summarize and highlight recent progress in the design, synthesis, biocompatibility evaluation and magnetic theranostic applications of IONPs, with a special focus on cancer treatment. Firstly, we provide an overview of the controlling synthesis strategies for fabricating zero-, one- and three-dimensional IONPs with different shapes, sizes and structures. Then, the and biocompatibility evaluation and biotranslocation of IONPs are discussed in relation to their chemo-physical properties including particle size, surface properties, shape and structure. Finally, we also highlight significant achievements in magnetic theranostic applications including magnetic resonance imaging (MRI), magnetic hyperthermia and targeted drug delivery. This review provides a background on the controlled synthesis, biocompatibility evaluation and applications of IONPs as cancer theranostic agents and an overview of the most up-to-date developments in this area.

In the present study, a facile one-pot hydrothermal method is introduced for preparation of hyaluronic acid-coated FeO nanoparticles (FeO@HA NPs) for theranostic applications. In the proposed method, hyaluronic acid acts simultaneously as a biocompatible coating layer and as a targeting ligand for CD44 receptor overexpressed on the surface of breast cancer cells. The obtained product with narrow hydrodynamic size distribution exhibited a high colloidal stability at physiological pH for more than three months. Cytotoxicity measurements indicated a negligible toxicity of the prepared sample against L929 normal cells. Preferential targeting of FeO@HA NPs to CD44-overexpressing cancer cells was studied by comparing the uptake of the prepared nanoparticles by MDA-MB-231 cancer cells (positive CD44 expression) and L929 normal cells (negative CD44 expression). Uptake of the FeO@HA NPs by MDA-MB-231 cells was found to be 4-fold higher than the normal cells. Also, the in vitro analysis showed that, the uptake of FeO@HA NPs by MDA-MB-231 breast cancer cells is significantly enhanced as compared to non-targeted dextran-coated FeO NPs. Moreover, the heat generation capability of the FeO@HA NPs for magnetic hyperthermia application was studied by exposing the prepared nanoparticles to different safe alternating magnetic fields (f = 120 kHz, H = 8, 10, and 12 kA/m). The intrinsic loss power obtained for FeO@HA NPs was about 3.5 nHm/kg, which is about 25-fold larger than that of obtained for commercial available FeO nanoparticles for biomedical applications. Good colloidal stability, biocompatibility, high heating efficacy, and targeting specificity to CD44 receptor-overexpressing cancer cells could make the FeO@HA NPs as a promising multifunctional platform for diagnosis and therapeutic applications.

The development of magnetic iron oxide nanoparticles with novel topological magnetic domain structures, such as the vortex-domain structure, is a promising strategy for improving the application performance of conventional superparamagnetic iron oxides while maintaining their good biocompatibility. Here, we fabricated a new kind of magnetic-vortex nanoparticles, i.e., ellipsoidal magnetite nanoparticles (EMPs), for cancer magnetic hyperthermia. The magnetization configurations and switching behaviours of the EMPs were analyzed by analytical simulations and Lorentz TEM, demonstrating the magnetic vortex structures of both single and coupled EMPs. The EMP treatment of 4T1 cells exposed to an alternating magnetic field (AMF) induced a significant decrease in the cell viability by ∼51.5%, which indicated a much higher cytotoxic effect in comparison with commercial superparamagnetic iron oxides (Resovist, ∼12.0%). In addition, the in vivo high efficacy of 4T1 breast tumor inhibition was also achieved by using EMP-mediated magnetic hyperthermia. Our results not only provide a new type of magnetic-vortex nanoparticles for efficient hyperthermia but also enrich the family of magnetic iron oxide nanoparticles for various biomedical applications.

Progress of thermal tumor therapies and their translation into clinical practice are limited by insufficient nanoparticle concentration to release therapeutic heating at the tumor site after systemic administration. Herein, the use of Janus magneto-plasmonic nanoparticles, made of gold nanostars and iron oxide nanospheres, as efficient therapeutic nanoheaters whose on-site delivery can be improved by magnetic targeting, is proposed. Single and combined magneto- and photo-thermal heating properties of Janus nanoparticles render them as compelling heating elements, depending on the nanoparticle dose, magnetic lobe size, and milieu conditions. In cancer cells, a much more effective effect is observed for photothermia compared to magnetic hyperthermia, while combination of the two modalities into a magneto-photothermal treatment results in a synergistic cytotoxic effect in vitro. The high potential of the Janus nanoparticles for magnetic guiding confirms them to be excellent nanostructures for in vivo magnetically enhanced photothermal therapy, leading to efficient tumor growth inhibition.

Isolation of cancer cells, bacteria, and viruses from peripheral blood has important applications in cancer diagnosis, therapy monitoring, and drug development. Magnetic particles functionalized with antibodies that target receptors of cancer cells have been shown to isolate such entities using magnetic field gradients. Here, we report enhancement in capture efficiency and specificity by engineering magnetic nanoparticles and integrating them with microfluidics for the enumeration of tumor cells. Nanoparticles were made from iron oxide, coated with poly(ethylene glycol), and conjugated through avidin-biotin chemistry with antibody specifically against epithelial cell adhesion molecule (EpCAM). On exposure of targeted nanoparticles to tumor cells, specific uptake by EpCAM-expressing tumor cells (e.g., BxPC3, a pancreatic cancer cell) was observed, whereas there was negligible uptake by cells with low EpCAM expression (e.g., CCRF-CEM, a leukemia cell). Using an arrangement of magnets called a Halbach array, capture efficiency and specificity towards BxPC3 cells tagged with magnetic nanoparticles were enhanced, compared to conditions without the magnetic field gradient and/or without magnetic nanoparticles, either in buffer or in whole blood. These results illustrate that engineered magnetic nanoparticles and their integration with microfluidics have great potential for tumor cell enumeration and cancer prognosis.

Novel Janus nanoparticles (J-NPs) are developed by using single iron oxide (FeO) nanoparticles as the core and hydrophobic/hydrophilic polymeric brushes as the cloak. Because of the superparamagnetism and asymmetric functionality of J-NPs, they are used as drug carriers and therapeutic agents for cancer chemotherapy and magnetic hyperthermia with a magnetic resonance imaging (MRI) guide. The asymmetric functionality is constituted of hydrophobic polymethyl methacrylate (PMMA) brushes and hydrophilic polyacrylic acid (PAA) brushes, which are 'grafting to' or 'grafting from' FeO nanoparticles via activators regenerated by electron transfer atom transfer radical polymerization. The terminal chains of PMMA and PAA brushes are coordinated with FeO nanoparticles, so PMMA/FeO/PAA J-NPs possess structural stability in solvents. Because of the brush-structure, PMMA/FeO/PAA J-NPs show high encapsulation efficiency (89.75 ± 2.35%) and loading capacity (8.95 ± 0.26%). Under the alternating magnetic field (AMF), drug-loaded J-NPs achieve the highest cell proliferation-inhibition ratio in the cell proliferation test in vitro and the tumor growth inhibition test in vivo compared to single chemotherapy or magnetic hyperthermia. Meanwhile, J-NPs show good T imaging.

The ultrasonication-triggered interfacial assembly approach was developed to synthesize magnetic Janus amphiphilic nanoparticles (MJANPs) for cancer theranostic applications, where the biocompatible octadecylamine is used as a molecular linker to mediate the interactions between hydrophobic and hydrophilic nanoparticles across the oil-water interface. The obtained Co cluster-embedded FeO nanoparticles-graphene oxide (CCIO-GO) MJANPs exhibited superior magnetic heating efficiency and transverse relaxivity, 64 and 4 times higher than that of commercial superparamagnetic iron oxides, respectively. The methodology has been applicable to nanoparticles of various dimensions (5-100 nm), morphologies (sphere, ring, disk, and rod), and composition (metal oxides, noble metal and semiconductor compounds, etc.), thereby greatly enriching the array of MJANPs. In vivo theranostic applications using the tumor-bearing mice model further demonstrated the effectiveness of these MJANPs in high-resolution multimodality imaging and high-efficiency cancer therapeutics. The ubiquitous assembly approach developed in the current study pave the way for on-demand design of high-performance Janus amphiphilic nanoparticles for various clinical diagnoses and therapeutic applications.

Despite the advances in molecularly targeted therapies, delivery across the blood-brain barrier (BBB) and the targeting of brain tumors remains a challenge. Like brain, bone is a common site of metastasis and requires therapies capable of discerning the tumor from its healthy cellular milieu. To tackle these challenges, we made a variation on the previously proposed concept of the earthicle and fabricated an aqueous, surfactant-free ferrofluid containing superparamagnetic iron oxide nanoparticles (SPIONs) coated with silicate mesolayers and carbon shells, having 13 nm in size on average. Nanoparticles were synthesized hydrothermally and characterized using a range of spectroscopic, diffractometric, hydrodynamic and electron microscopy techniques. The double coating on SPIONs affected a number of physicochemical and biological properties, including colloidal stability and cancer targeting efficacy. Nanoparticles decreased the viability of glioblastoma and osteosarcoma cells and tumors more than that of their primary and non-transformed analogues. They showed a greater preference for cancer cells because of a higher rate of uptake by these cells and a pronounced adherence to cancer cell membrane. Even in an ultralow alternate magnetic field, nanoparticles generated sufficient heat to cause tumor death. Nanoparticles in MDCK-MDR1 BBB model caused mislocalization of claudin-1 at the tight junctions, underexpression of ZO-1 and no effect on occludin-1 and transepithelial resistance. Nanoparticles were detected in the basolateral compartments and examination of LAMP1 demonstrated that nanoparticles escaped the lysosome, traversed the BBB transcellularly and localized to the optic lobes of the third instar larval brains of Drosophila melanogaster. The passage was noninvasive and caused no adverse systemic effects to the animals. In conclusion, these nanoparticulate ferrofluids preferentially bind to cancer cells and, hence, exhibit a greater toxicity in these cells compared to the primary cells. They are also effective against solid tumors in vitro, can cross the BBB in Drosophila, and are nontoxic based on the developmental studies of flies raised in ferrofluid-infused media. STATEMENT OF SIGNIFICANCE: We demonstrate that a novel, hydrothermally synthesized composite nanoparticle-based ferrofluid is effective in reducing the viability of osteosarcoma and glioblastoma cells in vitro, while having minimal effects on primary cell lines. In 3D tumor spheroids, nanoparticles greatly reduced the metastatic migration of cancer cells, while the tumor viability was reduced compared to the control group by applying magnetic hyperthermia to nanoparticle-treated spheroids. Both in vitro and in vivo models of the blood-brain barrier evidence the ability of nanoparticles to cross the barrier and localize to the brain tissue. These composite nanoparticles show great promise as an anticancer biomaterial for the treatment of different types of cancer and may serve as an alternative or addendum to traditional chemotherapies.

As the combination of photothermal therapy (PTT) with immunotherapy provides an effective strategy in cancer treatment, a magnetic nanoparticle delivery system was constructed to load indocyanine green (ICG) and immunostimulator R837 hydrochloride (R837) for spatio-temporally PTT/immunotherapy synergism in cancer. This delivery system is composed of FeO magnetic nanoparticles (MPs) as the core to load ICG and polyethylene glycol polyphenols (DPA-PEG) as the coating layer to load R837, which formed R837 loaded polyphenols coating ICG loaded magnetic nanoparticles (MIRDs). After intravenous injection, the formed MIRDs resulted in long circulation, magnetic resonance imaging (MRI) guides, and magnetic targeting. Once targeting to the tumor, the MIRDs with the near-infrared (NIR) irradiation caused tumor ablation and resulted in tumor-associated antigens releasing to induce the body's immunological response, which was markedly improved it to attack the tumors with the R837 releasing from the outer DPA-PEG. In this case, the synergism of the PTT and immunotherapy inhibited tumor growth, metastasis and recurrence, which resulted in potent anticancer therapeutic effects with few side effect.

Magnetic hyperthermia is a promising therapy for the localized treatment of cancer based on the exposure of magnetic nanoparticles to an external alternating magnetic field. In order to evaluate some of the mechanisms involved in the cellular damage caused by this treatment, two different 3D cell culture models were prepared using collagen, which is the most abundant protein of the extracellular matrix. The same amount of nanoparticles was added to cells either before or after their incorporation into the 3D structure. Therefore, in one model, particles were located only inside cells (In model), while the other one had particles both inside and outside cells (In&Out model). In the In&Out model, the hyperthermia treatment facilitated the migration of the particles from the outer areas of the 3D structure to the inner parts, achieving a faster homogeneous distribution throughout the whole structure and allowing the particles to gain access to the inner cells. The cell death mechanism activated by the magnetic hyperthermia treatment was different in both models. Necrosis was observed in the In model and apoptosis in the In&Out model 24 h after the hyperthermia application. This was clearly correlated with the amount of nanoparticles located inside the cells. Thus, the combination of both 3D models allowed us to demonstrate two different roles of the magnetic particles during the hyperthermia treatment: (i) The modulation of the cell death mechanism depending on the amount of intracellular particles and (ii) the disruption of the collagen matrix caused by the extracellular nanoparticles.

Cancer stem cells (CSCs) have been implicated in cancer recurrence and therapy resistance. Therefore, a CSC-targeted therapy that disrupts the maintenance and survival of CSCs may offer an effective approach in killing tumor cells in primary tumors and preventing the metastasis caused by CSCs. Nanoparticles (NPs)-based thermotherapy and/or chemotherapy are promising therapeutic methods for cancer treatment. A silica-based multifunctional NP system was present, which encapsulated a chemotherapeutic agent and magnetic cores and coated with a specific antibody against the lung CSCs. The efficacy of this novel therapeutic strategy was systematically studied both and by simultaneous activating the combined thermotherapy and chemotherapy CSC-targeted NPs. These NPs were systematically administered and activated for targeted chemotherapy and thermotherapy by using an externally applied alternating magnetic field (AMF). The antibody-modified NPs targeted to lung CSCs with enhanced cellular uptake and extended accumulation in tumor . Up to 98% of lung CSCs was killed with 30-min application of AMF, due to the combined effects of hyperthermia and chemotherapeutic drug treatment. In models, this combined therapy significantly suppressed tumor growth and metastasis in lung CSC xenograft-bearing mice, with minimal side effects and adverse effects. With good biocompatibility and targeting capability, the nanodrug delivery system may offer a promising clinical platform for the combined thermotherapy and chemotherapy. This work demonstrated the feasibility of developing multifunctional nanomedicine targeting CSCs for effective cancer treatment.

Two major technical challenges of magnetic hyperthermia are quantitative assessment of agent distribution during and following administration and achieving uniform heating of the tumor at the desired temperature without damaging the surrounding tissues. In this study, we developed a multimodal MRI/MPI theranostic agent with active biological targeting for improved magnetic hyperthermia therapy (MHT). First, by systematically elucidating the magnetic nanoparticle magnetic characteristics and the magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) signal enhancement effects, which are based on the magnetic anisotropy, size, and type of nanoparticles, we found that 18 nm iron oxide NPs (IOs) could be used as superior nanocrystallines for high performance of MRI/MPI contrast agents in vitro. To improve the delivery uniformity, we then targeted tumors with the 18 nm IOs using a tumor targeting peptide, CREKA. Both MRI and MPI signals showed that the targeting agent improves the intratumoral delivery uniformity of nanoparticles in a 4T1 orthotopic mouse breast cancer model. Lastly, the in vivo antitumor MHT effect was evaluated, and the data showed that the improved targeting and delivery uniformity enables more effective magnetic hyperthermia cancer ablation than otherwise identical, nontargeting IOs. This preclinical study of image-guided MHT using cancer-targeting IOs and a novel MPI system paves the way for new MHT strategies.

Hyperthermia-increasing temperature of cancerous tissue for a short period of time-is considered as an effective treatment for various cancer types such as malignant bone tumors. Superparamagnetic and ferromagnetic particles have been studied for their hyperthermic properties in treating various types of cancers. The activation of magnetic nanoparticles by an alternating magnetic field is currently being explored as a technique for targeted therapeutic heating of different tumors and is being studied as an adjuvant to conventional chemotherapy and radiation therapy. In the case of bone cancers, to increase the efficiency of treatment in the hyperthermia therapy, employed materials should support bone regeneration as well. Magnetite is one of the most attractive magnetic nanoceramics used in hyperthermia application. However, biocompatibility and bioactivity of this material have raised questions. There is a high demand for extremely efficient hyperthermia materials which are equally biocompatible to non-tumor cells and tissues. We report the development of a biocompatible and bioactive material with desirable magnetic properties that show excellent hyperthermia properties and can be used for destruction of the cancerous tissue in addition to supporting tissue regeneration for treatment of bone tumors. In the current study, iron (Fe)-containing HT nanostructured material was prepared, and its biocompatibility, bioactivity, and hyperthermia abilities were studied. The developed materials showed effective hyperthermic properties with increased biocompatibility as compared to magnetite.

Colloidally stable nanoparticles-based magnetic agents endowed with very high relaxivity and specific absorption rate are extremely desirable for efficient magnetic resonance imaging and magnetic hyperthermia, respectively. Here, we report a water dispersible magnetic agent consisting of zinc-doped superparamagnetic iron oxide nanoparticles (i.e., Zn-SPIONs) of 15 nm size with high saturation magnetization coated with an amphiphilic polymer for effective magnetic resonance imaging and magnetic hyperthermia of glioblastoma cells. These biocompatible polymer-coated Zn-SPIONs had 24 nm hydrodynamic diameter and exhibited high colloidal stability in various aqueous media, very high transverse relaxivity of 471 mM s, and specific absorption rate up to 743.8 W g, which perform better than most iron oxide nanoparticles reported in the literature, including commercially available agents. Therefore, using these polymer-coated Zn-SPIONs even at low concentrations, T-weighted magnetic resonance imaging and moderate magnetic hyperthermia of glioblastoma cells under clinically relevant magnetic field were successfully implemented. In addition, the results of this in vitro study suggest the superior potential of Zn-SPIONs as a theranostic nanosystem for brain cancer treatment, simultaneously acting as a contrast agent for magnetic resonance imaging and a heat mediator for localized magnetic hyperthermia.