Magnetic Thermal Ablation Research Articles

Microspheres-mediated magnetic thermal ablation combined with immune checkpoint blockade therapy for liver cancer

Hepatocellular carcinoma (HCC) are some of the most difficult malignant tumors to treat, due to their high rates of metastasis and recurrence. Image-guided percutaneous ablation, which serves as an important means in HCC treatment. However, drawbacks such as puncture injury, metastasis, and a limited ablation range still exist. Therefore, A highly effective and non-invasive magnetic thermal ablation (MTA) scheme for HCC was proposed by precisely embolizing magnetic microspheres into tumor-feeding arteries. In this study, polyacrylamide (PAM) and ferric oxide (Fe3O4) were utilized to prepare uniformly sized PAM@Fe3O4 microspheres with excellent eddy current heating effects. Additionally, a combined approach of MTA and immunotherapy was suggested. MTA combined with immune checkpoint blockade therapy efficiently ablated primary tumors and inhibited simulated metastatic tumors in mice. Further arterial embolization experiments in rabbit ears and renal arteries demonstrated the effective retention of PAM@Fe3O4 microspheres in blood vessels for MTA. Finally, we successfully applied PAM@Fe3O4 microspheres for efficient MTA therapy in a rabbit VX2 in situ liver tumor model. The aim of research is to provide new strategies for clinical HCC treatment, promoting the transition from image-guided percutaneous minimally invasive ablation to noninvasive ablation. This significant transition holds the potential for clinical applicability.

Facile preparation of novel type polymethyl methacrylate/CoFe2O4/BNNS composite cements and their caloric performance in alternating magnetic fields

AbstractMagnetic hyperthermia generated by functionalized bone cement is a promising approach to treat postosteocarcinoma cancer regeneration. However, it is crucial to minimize the magnetic field intensity using localized high‐caloric‐generating nanoparticles to avoid the potential hazards of electromagnetic field exposure to living organisms. Herein, in situ hydrothermally synthesized CoFe2O4 (CoFe) nanoparticles and boron nitride nanosheet (BNNS)–supported CoFe complexes (BNCoFe) are incorporated into polymethyl methacrylate (PMMA) cement to prepare a composite implant with high‐intensity magnetic–thermal performance and safety. The results show that the CoFe nanoparticles (size = ~70 nm) anchored on BNNS surfaces exhibit a maximum magnetic–thermal ablation temperature of ~42°C within 50 s under an alternating magnetic field of 400 KHz (field frequency) and 30 Oe (field intensity) in vitro. Furthermore, the incorporation of BNNSs into the PMMA matrix notably increases the thermal conductivity of PMMA from 0.07 to 0.25 W mK−1 and improves its mechanical properties (compressive strength increases from 74.0 ± 1.6 to 81.0 ± 1.0 MPa), which is attributed to the crystalline structure of BNNSs in the PMMA matrix. Inductively coupled plasma analysis shows a considerably reduced Co2+ ion release from PMMA/BNCoFe, indicating its potential as a safe implantation material for hyperthermia treatment.

Biodegradable magnesium alloy with eddy thermal effect for effective and accurate magnetic hyperthermia ablation of tumors.

Magnetic hyperthermia therapy (MHT) is able to ablate tumors using an alternating magnetic field (AMF) to heat up magnetocaloric agents (e.g. magnetic nanoparticles) administered into the tumors. For clinical applications, there is still a demand to find new magnetocaloric agents with strong AMF-induced heating performance and excellent biocompatibility. As a kind of biocompatible and biodegradable material, magnesium (Mg) and its alloys have been extensively used in the clinic as an implant metal. Herein, we discovered that the eddy thermal effect of the magnesium alloy (MgA) could be employed for MHT to effectively ablate tumors. Under low-field-intensity AMFs, MgA rods could be rapidly heated, resulting in a temperature increase in nearby tissues. Such AMF-induced eddy thermal heating of MgA could not only be used to kill tumor cells in vitro, but also be employed for effective and accurate ablation of tumors in vivo. In addition to killing tumors in mice, we further demonstrated that VX2 tumors of much larger sizes growing in rabbits after implantation of MgA rods could also be eliminated after exposure to an AMF, illustrating the ability of MgA-based MHT to kill large-sized tumors. Moreover, the implanted MgA rods showed excellent biocompatibility and ∼20% of their mass was degraded within three months. Our work thus discovered for the first time that non-magnetic biodegradable MgA, an extensively used implant metal in clinic, could be used for effective magnetic thermal ablation of tumors under a low-field-intensity AMF. Such a strategy could be readily translated into clinical use.

PMMA-Fe3O4 for internal mechanical support and magnetic thermal ablation of bone tumors.

Background: Minimally invasive modalities are of great interest in the field of treating bone tumors. However, providing reliable mechanical support and fast killing of tumor cells to achieve rapid recovery of physical function is still challenging in clinical works.Methods: A material with two functions, mechanical support and magnetic thermal ablation, was developed from Fe3O4 nanoparticles (NPs) distributed in a polymethylmethacrylate (PMMA) bone cement. The mechanical properties and efficiency of magnetic field-induced thermal ablation were systematically and successfully evaluated in vitro and ex vivo. CT images and pathological examination were successfully applied to evaluate therapeutic efficacy with a rabbit bone tumor model. Biosafety evaluation was performed with a rabbit in vivo, and a cytotoxicity test was performed in vitro.Results: An NP content of 6% Fe3O4 (PMMA-6% Fe3O4, mFe: 0.01 g) gave the most suitable performance for in vivo study. At the 56-day follow-up after treatment, bone tumors were ablated without obvious side effects. The pathological examination and new bone formation in CT images clearly illustrate that the bone tumors were completely eliminated. Correspondingly, after treatment, the tendency of bone tumors toward metastasis significantly decreased. Moreover, with well-designed mechanical properties, PMMA-6%Fe3O4 implantation endowed tumor-bearing rabbit legs with excellent bio-mimic bone structure and internal support. Biosafety evaluation did not induce an increase or decrease in the immune response, and major functional parameters were all at normal levels.Conclusion: We have presented a novel, highly efficient and minimally invasive approach for complete bone tumor regression and bone defect repair by magnetic thermal ablation based on PMMA containing Fe3O4 NPs; this approach shows excellent heating ability for rabbit VX2 tibial plateau tumor ablation upon exposure to an alternating magnetic field (AMF) and provides mechanical support for bone repair. The new and powerful dual-function implant is a promising minimally invasive agent for the treatment of bone tumors and has good clinical translation potential.

Clinical effect of ultrasound-guided injection of biodegradable poly(lactic-co-glycolic acid)-Fe3O4 in situ implant for magnetic thermal ablation in treatment of nude mice with human liver cancer SMMC-7721 cells

Objective: To prepare the Fe3O4-loaded biodegradable liquid-solid phase inversion poly(lactic-co-glycolic acid) (PLGA) in situ implant for ultrasound-guided injection into nude mouse tumor model, and to investigate its clinical effect in thermomagnetic treatment of nude mice with human liver cancer SMMC-7721 cells in an alternating magnetic field. Methods: An in situ implant containing 10% Fe3O4 was prepared, and 50 μl Fe3O4-PLGA-NMP gel was injected into the subcutaneous tissue of Kunming mice. The degradation of this material was observed for 2 consecutive months, and the changes in body weight were recorded. HE staining and Prussian blue staining were performed for the heart, liver, spleen, lung, and kidney of Kunming mice. Fresh ex vivo bovine liver was taken and cut into cubes with a dimension of 2 cm×2 cm×2 cm and then 50 μl Fe3O4-PLGA-NMP gel was injected; after phase inversion, the cubes of ex vivo bovine liver were heated for 1, 2, 3, 4, and 5 minutes, respectively, and then cut open for observing the range of ablation; HE staining was also performed. Micro-CT scan was performed after ultrasound-guided injection of 50 μl Fe3O4-PLGA gel into the tumors of the nude mice, and then the nude mice were divided into treatment group and control group. The mice in the treatment group were given thermomagnetic treatment for 3 minutes, and tumor growth was observed daily. Results: The biodegradation of Fe3O4-PLGA-NMP implant showed that the subcutaneously injected material was gradually metabolized at 2 weeks after injection and that the nude mice were in good condition. The bovine liver ablation experiment showed that the range of ablation of 50 μl Fe3O4-PLGA implant reached 1.46 ± 0.11 cm. HE staining showed that part of bovine liver had coagulative necrosis. The phase inversion experiment of Fe3O4-PLGA gel showed quick liquid-solid phase inversion of the material after injection into the tumor, and the process of liquid-solid phase inversion could be monitored by ultrasound and CT. The detachment and incrustation of the tumor started at 2 days after treatment, the wound started to heal 15 days later, and the tumor tissue disappeared completely. Conclusion: Ultrasound-guided injection of biodegradable Fe3O4-PLGA in situ implant combined with magnetic thermal ablation can effectively treat human liver cancer SMMC-7721 cells in nude mice.

Thermosensitive/superparamagnetic iron oxide nanoparticle-loaded nanocapsule hydrogels for multiple cancer hyperthermia.

Magnetic hyperthermia therapy (MHT) has been explored as an efficient and non-invasive treatment for cancer. However, the short retention time of magnetic nanoparticles localized within tumor targets hinders its potential for repeatable treatment. We report herein on the development of an injectable, biodegradable, thermosensitive and superparamagnetic iron oxide nanoparticle-loaded nanocapsule hydrogels (SPION-NHs) system for multiple MHT and long-term magnetic resonance imaging (MRI) contrast. Transmission electron microscopic images showed the core-shell structure of self-assembled poly(organophosphazene) nanocapsules and multiple embedded SPIONs within the core. The SPION-loaded nanocapusule solution can be transformed into hydrogel form at body temperature via the hydrophobic interaction. The cancer cells were killed efficiently using multiple MHT at moderate temperature through necrosis, as compared to single MHT-induced apoptosis. More than three weeks retention of SPIONs within tumors after a single injection of SPION-NHs facilitated successful multiple MHT, which was monitored by T2-weighted MRI. Furthermore, excellent invivo anti-cancer effect was observed after four cycles of MHT without severe damage on the surrounding healthy tissues, which was in contrast to single magnetic thermal ablation.

In vivo monitoring of magnetic nanoparticle quantity in tumor bearing mice by multichannel magnetorelaxometry for thermal ablation studies

Event Abstract Back to Event In vivo monitoring of magnetic nanoparticle quantity in tumor bearing mice by multichannel magnetorelaxometry for thermal ablation studies Heike Richter1*, Melanie Kettering2, Frank Wiekhorst1, Olaf Kosch1, Uwe Steinhoff1, Kay Schwarz1, Peter Zirpel1, Ingrid Hilger2 and Lutz Trahms1 1 Physikalisch-Technische Bundesanstalt, Germany 2 University Hospital, Institute of Diagnostic and Interventional Radiology, Germany In magnetic thermal ablation, superparamagnetic iron oxide nanoparticles (MNP) that are accumulated in a tumor are exposed to an externally applied alternating magnetic field and generate heat, thereby inactivating cancer cells with minimal side-effects to the normal tissue. The intratumoral quantity of MNP needs to be thoroughly controlled to govern adequate heat production in the carcinoma region. Here, we investigate the capability of magnetorelaxometry (MRX) for the in vivo quantification of MNP accumulation in the tumor region and, moreover, the feasibility of non-invasive, non-contact monitoring the MNP uptake in freely moving SCID-conscious mice. We examined a BT-474 adenocarcinoma bearing mouse, which previously got an intratumoral injection of MNP (fluidMAG-D, chemicell GmbH, Berlin) followed by a thermal ablation treatment 24h after MNP injection. Using a 304-multichannel biomagnetic SQUID system in a magnetically shielded room, we performed MRX measurements of the mouse in the pre and post phase of thermal ablation. The mouse was magnetized using a Helmholtz coil (d 85 cm) with a magnetic field of 1.0 mT. The relaxation of the magnetic moment of MNP after switching off the magnetic field was measured for 90 s. We present results of a magnetic dipole model fit applying a Levenberg-Marquardt algorithm. In the presence of motion, it was therewith feasible to obtain position and magnitude of the magnetic moment and hence to quantify the nanoparticle accumulation in the mouse. The findings of our methodical study demonstrate that magnetorelaxometry is well-suited to monitor quantitatively the MNP accumulation without anesthesia before and after cancer therapy by magnetic heating, being an important precondition for treatment success. Conference: Biomag 2010 - 17th International Conference on Biomagnetism , Dubrovnik, Croatia, 28 Mar - 1 Apr, 2010. Presentation Type: Poster Presentation Topic: Nanoparticles, Biosusceptometry and Effects of Magnetic Fields Citation: Richter H, Kettering M, Wiekhorst F, Kosch O, Steinhoff U, Schwarz K, Zirpel P, Hilger I and Trahms L (2010). In vivo monitoring of magnetic nanoparticle quantity in tumor bearing mice by multichannel magnetorelaxometry for thermal ablation studies. Front. Neurosci. Conference Abstract: Biomag 2010 - 17th International Conference on Biomagnetism . doi: 10.3389/conf.fnins.2010.06.00391 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Apr 2010; Published Online: 08 Apr 2010. * Correspondence: Heike Richter, Physikalisch-Technische Bundesanstalt, Berlin, Germany, heike.richter@ptb.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Heike Richter Melanie Kettering Frank Wiekhorst Olaf Kosch Uwe Steinhoff Kay Schwarz Peter Zirpel Ingrid Hilger Lutz Trahms Google Heike Richter Melanie Kettering Frank Wiekhorst Olaf Kosch Uwe Steinhoff Kay Schwarz Peter Zirpel Ingrid Hilger Lutz Trahms Google Scholar Heike Richter Melanie Kettering Frank Wiekhorst Olaf Kosch Uwe Steinhoff Kay Schwarz Peter Zirpel Ingrid Hilger Lutz Trahms PubMed Heike Richter Melanie Kettering Frank Wiekhorst Olaf Kosch Uwe Steinhoff Kay Schwarz Peter Zirpel Ingrid Hilger Lutz Trahms Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Magnetic Thermal Ablation Using Ferrofluids: Influence of Administration Mode on Biological Effect in Different Porcine Tissues

The purpose of this study was to compare the effects of magnetic thermal ablation in different porcine tissues using either a singular injection or a continuous infusion of superparamagnetic iron oxide nanoparticles. In the first setting samples of three ferrofluids containing different amounts of iron (1:171, 2:192, and 3:214 mg/ml) were singularly interstitially injected into specimens of porcine liver, kidney, and muscle (n = 5). Then the specimens were exposed to an alternating magnetic field (2.86 kA/m, 190 kHz) generated by a circular coil for 5 min. In the second experimental setup ferrofluid samples were continuously interstitially infused into the tissue specimens during the exposure to the magnetic field. To measure the temperature increase two fiber-optic temperature probes with a fixed distance of 0.5 cm were inserted into the specimens along the puncture tract of the injection needle and the temperature was measured every 15 s. Finally, the specimens were dissected, the diameters of the created thermal lesions were measured, and the volumes were calculated and compared. Compared to continuous infusion, a single injection of ferrofluids resulted in smaller coagulation volumes in all tissues. Significant differences regarding coagulation volume were found in kidney and muscle specimens. The continuous infusion technique led to more elliptically shaped coagulation volumes due to larger diameters along the puncture tract. Our data show the feasibility of magnetic thermal ablation using either a single interstitial injection or continuous infusion for therapy of lesions in muscle, kidney, and liver. Continuous infusion of ferrofluids results in larger zones of necrosis compared to a single injection technique.

Thermal ablation of tumors using magnetic nanoparticles: an in vivo feasibility study.

Feasibility of a new interventional procedure for the treatment of breast cancer called "magnetic thermal ablation" was examined under in vivo animal conditions. The method consists in the intratumoral application of iron oxide particles and the exposure of the breast to an alternating magnetic field, whereby the tumor is eliminated by heat. Human breast adenocarcinomas were implanted into 45 immunodeficient SCID mice. Defined magnetite particle masses (between 4 mg and 18 mg per 100 mg tumor tissue) were injected intratumorally. Approximately 20 minutes later, animals were exposed to an alternating current (AC) magnetic field (amplitude: 6.5 kA/m, frequency: 400 kHz) for 4 minutes while measuring the temperature at defined tumor positions and at the rectum. The method efficacy was determined by the following end points: the assessment of the deposited heat dosages (DHD) at the defined locations within the target. The DHD was defined as the area between the time-dependent temperature curves during treatments and the temperature level without heating; histologic examinations of tumor tissue after heating; and the evaluation of the particle wash-out from the tumor by determining the percentage of injected iron doses per g tissue of selected organs (atomic absorption spectrometry; 50 minutes postinjection). Temperature increases between 12 degrees C and 73 degrees C were registered at different tumor locations (tumor center and periphery). The corresponding DHD ranged between 40 degrees C and 262 degrees C x minutes. Regions of DHD underdosage (lower than approximately 47-61 degrees C x min) were observed in 8 of 36 tumors. 2.4% to 22.3% of the injected iron dose per g dried tissues other than the tumor was detected after 50 minutes postinjection. Histologic examinations showed the presence of early stages of coagulation necrosis in treated tumor cells. The data indicate that the proposed method allows the generation of localized heat spots at the tumor area. According to the histologic analysis and previous investigations the DHD were, in principle, high enough to kill tumor cells. The reasons for the presence of regions of temperature underdosage are discussed in the text. Special attention should be paid on the particle wash out in organs in the vicinity of the breast.