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The prognosis for Cholangiocarcinoma (CCA) is unfavorable, necessitating the development of new therapeutic approach such as magnetic hyperthermia therapy (MHT) which is induced by magnetic nano-particle (MNPs) drug to bridge the treatment gap. Given the deep location of CCA within the abdominal cavity and proximity to vital organs, accurately predict the individualized treatment effects and safety brought by the distribution of MNPs in tumor will be crucial for the advancement of MHT in CCA. The Mimics software was used in this study to conduct three-dimensional reconstruction of abdominal computed tomography (CT) and magnetic reso-nance imaging images from clinical patients, resulting in the generation of a realistic digital geometric model representing the human biliary tract and its adjacent structures. Subsequently, The COMSOL Multiphysics software was utilized for modeling CCA and calculating the heat transfer law resulting from the multi-regional distribution of MNPs in CCA. The temperature within the central region of irregular CCA measured approximately 46°C, and most areas within the tumor displayed temperatures surpassing 41°C. The temperature of the inner edge of CCA is only 39 ∼ 41℃, however, it can be ameliorated by adjusting the local drug concentration through simulation system. For CCA with diverse morphologies and anatomical locations, the multi-regional distribution patterns of intratumoral MNPs and a slight overlap of drug distribution areas synergistically enhance intratumoral temperature while ensuring treatment safety. The present study highlights the practicality and imperative of incorporating personalized intratumoral MNPs distribution strategy into clinical practice for MHT, which can be achieved through the development of an integrated simulation system which incorporates medical image data and numerical calculations.

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Precise and effective initiation of the apoptotic mechanism in tumor cells is one of the most promising approaches for the treatment of solid tumors. However, current techniques such as high-temperature ablation or gene editing suffer from the risk of damage to adjacent normal tissues. This study proposes a magnetothermal-induced CRISPR-Cas9 gene editing system for the targeted knockout of HSP70 and BCL2 genes, thereby enhancing tumor cell apoptosis. The magnetothermal nanoparticulate platform is composed of superparamagnetic ZnCoFe2O4@ZnMnFe2O4 nanoparticles and the modified polyethyleneimine (PEI) and hyaluronic acid (HA) on the surface, on which plasmid DNA can be effectively loaded. Under the induction of a controllable alternating magnetic field, the mild magnetothermal effect (42℃) not only triggers dual-genome editing to disrupt the apoptosis resistance mechanism of tumor cells but also sensitizes tumor cells to apoptosis through the heat effect itself, achieving a synergistic therapeutic effect. This strategy can precisely regulate the activation of the CRISPR-Cas9 system for tumor cell apoptosis without inducing significant damage to healthy tissues, thus providing a new avenue for cancer treatment.

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Invasive tumors are difficult to be completely resected in clinical surgery due to the lack of clear resection margins, which greatly increases the risk of postoperative recurrence. However, chemotherapy and radiotherapy as the traditional means of postoperative adjuvant therapy, are limited in postoperative applications, such as multi-drug resistance and low sensitivity, etc. Therefore, an engineered magnesium alloy rod is designed as a postoperative implant to completely remove postoperative residual tumor tissue and inhibit tumor recurrence by gas and mild magnetic hyperthermia therapy (MMHT). As a reactive metal, magnesium alloy responds to the acidic tumor microenvironment by continuously generating hydrogen. The in-situ generation of hydrogen not only protects the surrounding normal tissue, but also enables the magnesium alloy to achieve MMHT under low-intensity alternating magnetic field (AMF). Furthermore, the numerous reactive oxygen species (ROS) produced by heat stress will combine with nitric oxide (NO) generated in situ, to produce more toxic reactive nitrogen species (RNS) storm. In summary, engineered magnesium alloy can completely remove residual tumor tissue and inhibit tumor recurrence by MMHT and RNS storm under low-intensity AMF, and the biodegradability of magnesium alloy makes great potential for clinical application.

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While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered self-repairing autophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel (NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundant NO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn0.5Fe2.5O4 magnetic nanoparticles (MNPs) with high magnetic-heat conversion efficiency are synthesized and loaded into NO-Gel to obtain MNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability to perform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distribution and strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and this process is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over one month and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel at the tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NO effectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronously destroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26 colon tumors are completely eliminated without causing severe side-effects.

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A novel thermal-responsive ß-cyclodextrin-based magnetic hydrogel [ß-cyclodextrin-graft-poly(N-isopropylacrylamide)/Fe3O4 (ß-CD-g-PNIPAAm/Fe3O4)] was fabricated as a novel nanomedicine for chemo/hyperthermia treatment of cancer cells. Firstly, ß-CD was modified by maleic anhydride (MA) followed by copolymerization with NIPAAm monomer and thiol-end capped Fe3O4 nanoparticles (NPs) in the presence of a crosslinker through acrylamide-thiol polymerization system to afford a magnetic hydrogel. The saturation magnetization (δ s) value for developed hydrogel was determined to be 8.2 emu g-1. The hydrogel was physically loaded with an anticancer agent, doxorubicin hydrochloride (Dox). The encapsulation efficiency (EE) of drug into the hydrogel was obtained as 73 %. The system represented acceptable thermal-triggered drug release behavior that best fitted with Higuchi model, demonstrating the release of drug is mostly controlled by diffusion mechanism. The anticancer performance of the ß-CD-g-PNIPAAm/Fe3O4-Dox was evaluated using MCF7 cells by MTT-assay. In addition, flow cytometry analyses showed considerable cellular uptake of Dox in the cells treated with ß-CD-g-PNIPAAm/Fe3O4-Dox (∼70 %) compared to free Dox (∼28 %). As results, in time period of 48 h by combination of chemo- and hyperthermia-therapies, the developed system displayed greater anticancer efficiency than the free Dox.

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Despite laparoscopic-guided minimally invasive hepatectomy emerging as the primary approach for resecting hepatocellular carcinoma (HCC), there's still a significant gap in suitable biomaterials that seamlessly integrate with these techniques to achieve effective hemostasis and suppress residual tumors at the surgical margin. Electrospun films are increasingly used for wound closure, yet the employment of prefabricated electrospun films for hemostasis during minimally invasive HCC resection is hindered by prolonged operation times, complexity in implementation, limited visibility during surgery, and inadequate postoperative prevention of HCC recurrence. In this study, we integrated montmorillonite-iron oxide sheets into the PVP polymer framework, enhancing the resulting electrospun polyvinylpyrrolidone (PVP) /montmorillonite-iron oxide (MI) film (abbreviated as PMI) with robustness, hemostatic capability, and magnetocaloric properties. In contrast to the in vitro prefabricated electrospun films, the electrospun PMI film is designed to be formed in situ on liver wounds under laparoscopic guidance during hepatectomy. This design affords superior wound adaptability, facilitating meticulous wound closure and expeditious hemostasis, thereby simplifying the operative process and ultimately alleviating the workload of healthcare professionals. Moreover, when exposed to an alternating magnetic field, the film can efficiently ablate residual tumors, significantly augmenting the treatment efficacy of HCC. This article is protected by copyright. All rights reserved.

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Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.

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Magnetic hyperthermia therapy (MHT) is a promising treatment modality for brain tumors using magnetic nanoparticles (MNPs) locally delivered to the tumor and activated with an external alternating magnetic field (AMF) to generate antitumor effects through localized heating. Magnetic particle imaging (MPI) is an emerging technology offering strong signal-to-noise for nanoparticle localization. A scoping review was performed by systematically querying Pubmed, Scopus, and Embase. In total, 251 articles were returned, 12 included. Articles were analyzed for nanoparticle type used, MHT parameters, and MPI applications. Preliminary results show that MHT is an exciting treatment modality with unique advantages over current heat-based therapies for brain cancer. Effective application relies on the further development of unique magnetic nanoparticle constructs and imaging modalities, such as MPI, that can enable real-time MNP imaging for improved therapeutic outcomes.

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Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon-centered free radicals (R⋅) can inactivate NF-κB transcription by capping the active sites in both NF-κB and DNA. We construct a type of thermosensitive R⋅ initiator loaded amphiphilic nano-micelles to facilitate intracellular delivery of R⋅. At a temperature of 43 °C, the generated R⋅ engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF-κB through radical chain reaction. As a result, both NF-κB nuclear translocation and NF-κB-DNA binding are suppressed, leading to a remarkable NF-κB inhibition of up to 94.1 %. We have further applied R⋅ micelles in a clinical radiofrequency ablation tumor therapy model, showing remarkable NF-κB inactivation and consequently tumor metastasis inhibition. Radical capping strategy not only provides a method to solve the heat-sink effect in clinic tumor hyperthermia, but also suggests a new perspective for controllable modification of biomacromolecules in cancer therapy.

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Magnetic hyperthermia therapy (MHT) is a re-emerging treatment modality for brain tumors where magnetic nanoparticles (MNPs) are locally delivered to the brain and then activated with an external alternating magnetic field (AMF) to generate localized heat at a site of interest. Due to the recent advancements in technology and theory surrounding the intervention, clinical and pre-clinical trials have demonstrated that MHT may enhance the effectiveness of chemotherapy and radiation therapy (RT) for the treatment of brain tumors. The future clinical success of MHT relies heavily on designing MNPs optimized for both heating and imaging, developing reliable methods for the local delivery of MNPs, and designing AMF systems with integrated magnetic particle imaging (MPI) for use in humans. However, despite the progression of technological development, the clinical progress of MHT has been underwhelming. This review aims to summarize the current state-of-the-art of MHT and offers insight into the current barriers and potential solutions for moving MHT forward.

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Magnetic spinel ferrite nanoparticles (MSF-NPs) are potential candidates for biomedical applications, especially in cancer diagnosis and therapy due to their excellent physiochemical and magnetic properties. In the current study, MSF-NPs were fabricated by sol-gel auto combustion method. The crystal structure and surface morphology were confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The magnetic properties were studied by VSM (vibrating sample magnetometer). As increasing Gd3+ concentration, the saturation magnetization values decreased from (17.8-2.3) emu/g, while the coercivity decreased from (499-133) Oe at room temperature. Finally, the fabricated MSF-NPs were tested against anticancer activity by MTT assay. The IC50 = 21.27 µg/mL value was observed, showing the strong antiproliferative activity of these nanoparticles. These results suggested that the obtained MSF-NPs would be useful for remote-controlled hyperthermia therapy for cancer treatment and MRI application due to their excellent magnetic properties. These distinct properties make MSF-NPs most suitable for cancer treatment and bright Contrast Agents (T1-MRI).

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Large osseous void, postsurgical neoplastic recurrence, and slow bone-cartilage repair rate raise an imperative need to develop functional scaffold in clinical osteosarcoma treatment. Herein, a bionic bilayer scaffold constituting croconaine dye-polyethylene glycol@sodium alginate hydrogel and poly(l-lactide)/hydroxyapatite polymer matrix is fabricated to simultaneously achieve a highly efficient killing of osteosarcoma and an accelerated osteochondral regeneration. First, biomimetic osteochondral structure along with adequate interfacial interaction of the bilayer scaffold provide a structural reinforcement for transverse osseointegration and osteochondral regeneration, as evidenced by upregulated specific expressions of collagen type-I, osteopontin, and runt-related transcription factor 2. Meanwhile, thermal ablation of the synthesized nanoparticles and mitochondrial dysfunction caused by continuously released hydroxyapatite induce residual tumor necrosis synergistically. To validate the capabilities of inhibiting tumor growth and promoting osteochondral regeneration of our proposed scaffold, a novel orthotopic osteosarcoma model simulating clinical treatment scenarios of bone tumors is established on rats. Based on amounts of in vitro and in vivo results, an effective killing of osteosarcoma and a suitable osteal-microenvironment modulation of such bionic bilayer composite scaffold are achieved, which provides insightful implications for photonic hyperthermia therapy against osteosarcoma and following osseous tissue regeneration.

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Ischemic diseases due to arterial stenosis or occlusion are common and can have serious consequences if untreated. Therapeutic ultrasound like high-intensity focused ultrasound (HIFU) ablates tissues while low-intensity pulsed ultrasound (LIPU) promotes healing at relatively low temperatures. However, blood vessel cooling effect and reduced flow in ischemia impact temperature distribution and ultrasonic treatment efficacy. This work established a rabbit limb ischemia model by ligating the femoral artery, measuring vascular changes and temperature rise during LIPU exposures. Results showed the artery diameter was narrowed by 46.2% and the downstream velocity was reduced by 51.3% after ligation. Finite element simulations verified that the reduced flow velocity impaired heat dissipation, enhancing LIPU-induced heating. Simulation results also suggested the temperature rise was almost related linearly to vessel diameter but decayed exponentially with the increasing flow velocity. Findings indicate that the proposed model could be used as an effectively tool to model the heating effects in ischemic tissues during LIPU treatment. This research on relating varied ischemic flow to LIPU-induced thermal effects is significant for developing safe and efficacious clinical ultrasound hyperthermia treatment protocols for the patients with ischemic diseases.

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The therapeutic efficacy of bone tumor treatment is primarily limited by inadequate tumor resection, resulting in recurrence and metastasis, as well as the deep location of tumors. Herein, an injectable doxorubicin (DOX)-loaded magnetic alginate hydrogel (DOX@MAH) was developed to evaluate the efficacy of an alternating magnetic field (AMF)-responsive, chemothermal synergistic therapy for multimodality treatment of bone tumors. The prepared hydrogel exhibits a superior drug-loading capacity and a continuous DOX release. This multifunctionality can be attributed to the combined use of DOX for chemotherapy and iron oxide nanoparticle-containing alginate hydrogels as magnetic hyperthermia agents to generate hyperthermia for tumor elimination without the limit on penetration depth. Moreover, the hydrogel can be formed when in contact with the calcium ions, which are abundant in bone tissues; therefore, this hydrogel could perfectly fit the bone defects caused by the surgical removal of the bone tumor tissue, and the hydrogel could tightly attach the surgical margin of the bone to realize a high efficacy residual tumor tissue elimination treated by chemothermal synergistic therapy. The hydrogel demonstrates excellent hyperthermia performance, as evidenced by in vitro cytotoxicity tests on tumor cells. These tests reveal that the combined therapy based on DOX@MAH under AMF significantly induces cell death compared to single magnetic hyperthermia or chemotherapy. In vivo antitumor effects in tumor-bearing mice demonstrate that DOX@MAH injection at the tumor site effectively inhibits tumor growth and leads to tumor necrosis. This work not only establishes an effective DOX@MAH system as a synergistic chemothermal therapy platform for treating bone tumors but also sheds light on the application of alginate to combine calcium ions of the bone to treat bone defect diseases.

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Magnetic hyperthermia therapy (MHT) has garnered immense interest due to its exceptional spatiotemporal specificity, minimal invasiveness and remarkable tissue penetration depth. Nevertheless, the limited magnetothermal heating capability and the potential toxicity of metal ions in magnetic materials based on metallic elements significantly impede the advancement of MHT. Herein, we introduce the concept of nonmetallic materials, with graphite (Gra) as a proof of concept, as a highly efficient and biocompatible option for MHT of tumors in vivo for the first time. The Gra exhibits outstanding magnetothermal heating efficacy owing to the robust eddy thermal effect driven by its excellent electrical conductivity. Furthermore, being composed of carbon, Gra offers superior biocompatibility as carbon is an essential element for all living organisms. Additionally, the Gra boasts customizable shapes and sizes, low cost, and large-scale production capability, facilitating reproducible and straightforward manufacturing of various Gra implants. In a mouse tumor model, Gra-based MHT successfully eliminates the tumors at an extremely low magnetic field intensity, which is less than one-third of the established biosafety threshold. This study paves the way for the development of high-performance magnetocaloric materials by utilizing nonmetallic materials in place of metallic ones burdened with inherent limitations.

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Relapse and unresectability have become the main obstacle for further improving hepatocellular carcinoma (HCC) treatment effect. Currently, single therapy for HCC in clinical practice is limited by postoperative recurrence, intraoperative blood loss and poor patient outcomes. Multidisciplinary therapy has been recognized as the key to improving the long-term survival rate for HCC. However, the clinical application of HCC synthetic therapy is restricted by single functional biomaterials. In this study, a magnetic nanocomposite hydrogel (CG-IM) with iron oxide nanoparticle-loaded mica nanosheets (Iron oxide nanoparticles@Mica, IM) is reported. This biocompatible magnetic hydrogel integrated high injectability, magnetocaloric property, mechanical robustness, wet adhesion, and hemostasis, leading to efficient HCC multidisciplinary therapies including postoperative tumor margin treatment and percutaneous locoregional ablation. After minimally invasive hepatectomy of HCC, the CG-IM hydrogel can facilely seal the bleeding hepatic margin, followed by magnetic hyperthermia ablation to effectively prevent recurrence. In addition, CG-IM hydrogel can inhibit unresectable HCC by magnetic hyperthermia through the percutaneous intervention under ultrasound guidance.

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Magnetic nanoparticles (MNPs) are promising in tumor treatments due to their capacity for magnetic hyperthermia therapy (MHT), chemodynamic therapy (CDT), and immuno-related therapies, but still suffer from unsatisfactory tumor inhibition in the clinic. Insufficient hydrogen peroxide supply, glutathione-induced resistance, and high-density extracellular matrix (ECM) are the barriers. Herein, we hierarchically decorated MNPs with disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx) to form a nanosystem (MNPs-SS-R-GOx). Its outer GOx layer not only enhanced the H2O2 supply to produce .OH by Fenton reaction, but also generated stronger oxidants (ONOO-) together with the interfaced R layer. The inner S-S layer consumed glutathione to interdict its reaction with oxidants, thus enhancing CDT effects. Importantly, the generated ONOO- tripled the MMP-9 expression to induce ECM degradation, enabling much deeper penetration of MNPs and benefiting CDT, MHT, and immunotherapy. Finally, the MNPs-SS-R-GOx demonstrated a remarkable 91.7% tumor inhibition in vivo. STATEMENT OF SIGNIFICANCE: Magnetic nanoparticles (MNPs) are a promising tumor therapeutic agent but with limited effectiveness. Our hierarchical MNP design features disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx), which boosts H2O2 supply for ·OH generation in Fenton reactions, produces potent ONOO-, and enhances chemodynamic therapy via glutathione consumption. Moreover, the ONOO- facilitates the upregulation of matrix metalloprotein expression beneficial for extracellular matrix degradation, which in turn enhances the penetration of MNPs and benefits the antitumor CDT/MHT/immuno-related therapy. In vivo experiments have demonstrated an impressive 91.7% inhibition of tumor growth. This hierarchical design offers groundbreaking insights for further advancements in MNP-based tumor therapy. Its implications extend to a broader audience, encompassing those interested in material science, biology, oncology, and beyond.

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Nowadays, magnetic nanoparticles (MNPs) are applied in numerous fields, especially in biomedical applications. Since biofluidic samples and biological tissues are nonmagnetic, negligible background signals can interfere with the magnetic signals from MNPs in magnetic biosensing and imaging applications. In addition, the MNPs can be remotely controlled by magnetic fields, which make it possible for magnetic separation and targeted drug delivery. Furthermore, due to the unique dynamic magnetizations of MNPs when subjected to alternating magnetic fields, MNPs are also proposed as a key tool in cancer treatment, an example is magnetic hyperthermia therapy. Due to their distinct surface chemistry, good biocompatibility, and inducible magnetic moments, the material and morphological structure design of MNPs has attracted enormous interest from a variety of scientific domains. Herein, a thorough review of the chemical synthesis strategies of MNPs, the methodologies to modify the MNPs surface for better biocompatibility, the physicochemical characterization techniques for MNPs, as well as some representative applications of MNPs in disease diagnosis and treatment are provided. Further portions of the review go into the diagnostic and therapeutic uses of composite MNPs with core/shell structures as well as a deeper analysis of MNP properties to learn about potential biomedical applications.

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Obesity has become an ongoing global crisis, since it increases the risks of cardiovascular disease, type 2 diabetes, fatty liver, cognitive decline, and some cancers. Adipose tissue is closely associated with the disorder of lipid metabolism. Several efforts have been made toward the modulation of lipid accumulation, but have been hindered by poor efficiency of cellular uptake, low safety, and uncertain effective dosage. Herein, we design an Fe3O4microsphere-doped composite hydrogel (Fe3O4microspheres @chitosan/ß-glycerophosphate/collagen), termed as Fe3O4@Gel, as the magnetocaloric agent for magnetic hyperthermia therapy (MHT), aiming to promote lipolysis in white adipocytes. The experimental results show that the obtained Fe3O4@Gel displays a series of advantages, such as fast sol-gel transition, high biocompatibility, and excellent magneto-thermal performance. MHT, which is realized by Fe3O4@Gel subjected to an alternating magnetic field, leads to reduced lipid accumulation, lower triglyceride content, and increased mitochondrial activity in white adipocytes. This work shows that Fe3O4@Gel-mediated MHT can effectively promote lipolysis in white adipocytesin vitro, which provides a potential approach to treat obesity and associated metabolic disorders.

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Traditional cancer treatments are ineffective and cause severe adverse effects. Thus, the development of chemodynamic therapy (CDT) has the potential for in situ catalysis of endogenous molecules into highly toxic species, which would then effectively destroy cancer cells. However, the shortage of high-performance nanomaterials hinders the broad clinical application of this approach. In present study, an effective therapeutic platform was developed using a simple hydrothermal method for the in-situ activation of the Fenton reaction within the tumor microenvironment (TME) to generate substantial quantities of •OH and ultimately destroy cancer cells, which could be further synergistically increased by photothermal therapy (PHT) and magnetic hyperthermia (MHT) aided by FeMoO4 nanorods (NRs). The produced FeMoO4 NRs were used as MHT/PHT and Fenton catalysts. The photothermal conversion efficiency of the FeMoO4 NRs was 31.75 %. In vitro and \ experiments demonstrated that the synergistic combination of MHT/PHT/CDT notably improved anticancer efficacy. This work reveals the significant efficacy of CDT aided by both photothermal and magnetic hyperthermia and offers a feasible strategy for the use of iron-based nanoparticles in the field of biomedical applications.

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