Magnetothermal Therapy Research Articles

Transition metal ion-doped ferrites nanoparticles for bioimaging and cancer therapy

Magnetic nanoparticles (MNPs) have been extensively researched and implemented in biomedicine for more than half a century due to their non-invasive nature, ease of temporal and spatial manipulation, and considerable biocompatibility. However, the complex magnetic behaviour of MNPs is influenced by several parameters (e.g., particle size, shape, composition, core-shell structure, etc.), among which the amount of transition metal doping plays an important factor. For this reason, the doping of ferrite with transition metals has been used as an effective strategy to precisely tailor MNPs to achieve satisfactory performance in biomedical applications. In this review, we first introduced the main properties of coordinated MNPs (including magnetic moment and saturated magnetisation) and provide a comprehensive overview of the mechanistic studies related to the doping of transition metal ions into ferrite to precisely modulate its magnetic properties. We also highlighted the potential mechanisms and recent advances in transition metal ion-doped MNPs (TMNPs) for bioimaging (magnetic resonance imaging and magnetic particle imaging) and tumour therapy (e.g., magneto-mechanical killing, magnetothermal therapy, and drug delivery). Finally, we summarised the current challenges and future trends of TMNPs in the biomedical field based on the latest advances by researchers.

Graphene Oxide-loaded magnetic nanoparticles within 3D hydrogel form High-performance scaffolds for bone regeneration and tumour treatment

The treatment of tumour-related bone defects should ideally combine bone regeneration with tumour treatment. Additive manufacturing (AM) could feasibly place functional bone-repair materials within composite materials with functional-grade structures, giving them bone repair and anti-tumour effects. Magnetothermal therapy is a promising non-invasive method of tumour treatment that has attracted increasing attention. In this study, we prepared novel hydrogel composite scaffolds of polyvinyl alcohol/sodium alginate/hydroxyapatite (PVA/SA/HA) at low temperature via AM. The scaffolds were loaded with various concentrations of magnetic graphene oxide (MGO) @Fe3O4 nanoparticles. The scaffolds were characterised by fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and thermal gravimetric analysis (TGA), which showed that the scaffolds have good moulding qualities and strong hydrogen bonding between the MGO/PVA/SA/HA components. TGA analysis demonstrated the expected thermal stability of the MGO and scaffolds. Thermal effects can be adjusted by varying the contents of MGO and the strength of an external alternating magnetic field. The prepared MGO hydrogel composite scaffolds enhance biological functions and support bone mesenchymal stem cell differentiation in vitro. The scaffolds also show favourable anti-tumour characteristics with effective magnetothermal conversion in vivo.

Regulation of ID4 In Vivo for Efficient Magnetothermal Therapy of Breast Cancer

AbstractMagnetic nanoparticles (MNPs) mediated magnetothermal therapy (MTT) has been proven as a promising modality for tumor treatment. However, the low therapeutic efficacy presents a major obstacle to its mass adoption. The Authors proposed to increase the therapeutic efficacy of MTT through the manipulation of magnetothermal‐related gene expression. ID4, a member of inhibitors of differentiation (ID) protein family, is identified to be downregulated in intracellular MTT (in‐MTT)‐treated MCF‐7 breast cancer cells according to the whole transcriptome sequencing. Interestingly, this occurrence is not observed in the exogenous MTT‐treated cells. More importantly, ID4‐silenced tumor cells show significantly decreased cell viability after in‐MTT, whereas ID4‐overexpressed cells exhibit more resistance to the MTT. This effect is also observed in other malignant breast cells derived from the human mammary gland. Furthermore, ID4 siRNA‐loaded superparamagnetic iron oxide nanoparticles are developed and delivered them to breast cancer xenografted nude mice. It is found that the synergistic combination of ID4 gene silencing and in‐MTT greatly inhibited the tumor growth and the efficacy of tumor volume inhibition is > 98%. This study, for the first time, provides the possibility of the sensitization of breast cancer cells for efficient MTT via molecular manipulation of cell signaling.

Magneto-Based Synergetic Therapy for Implant-Associated Infections via Biofilm Disruption and Innate Immunity Regulation.

Implant‐associated infections (IAIs) are a common cause of orthopedic surgery failure due to microbial biofilm‐induced antibiotic‐resistance and innate immune inactivation. Thus, the destruction of microbial biofilm plays a key role in reducing IAIs. Herein, first, a magneto‐based synergetic therapy (MST) is proposed and demonstrated against IAIs based on biofilm destruction. Under an alternating magnetic field (AMF), CoFe2O4@MnFe2O4 nanoparticles (MNPs), with a rather strong magnetic hyperthermal capacity, can generate sufficient thermal effect to cause dense biofilm dispersal. Loosened biofilms provide channels through which nitrosothiol‐coated MNPs (MNP‐SNOs) can penetrate. Subsequently, thermosensitive nitrosothiols rapidly release nitric oxide (NO) inside biofilms, thus efficiently killing sessile bacteria under the magnetothermal effect of MNPs. More importantly, MNP‐SNOs can trigger macrophage‐related immunity to prevent the relapse of IAIs by exposing the infected foci to a consistent innate immunomodulatory effect. The notable anti‐infection effect of this nanoplatform is also confirmed in a rat IAI model. This work presents the promising potential of combining magnetothermal therapy with immunotherapy, for the effective and durable control and elimination of IAIs.

Second near-infrared photothermal materials for combinational nanotheranostics.

Second near-infrared photothermal therapy (NIR-II PTT, 1000-1500 nm) has recently emerged as a new phototherapeutic modality with the advantages of deeper penetration, less energy dissipation and minimal normal-tissue toxicity over traditional first NIR PTT (750-1000 nm). However, suboptimal photothermal conversion and limited therapeutic efficacy remain the major challenges for NIR-II PTT. With the convergence in materials science, nanomedicine and biology, multifunctional NIR-II photothermal inorganic or organic materials have been extensively developed to combine NIR-II PTT with other therapeutic modalities for improved efficacies in treating life-threatening diseases including cancer and infection. This review summarizes the recent advances of NIR-II photothermal combinational theranostics pertinent to chemotherapy, immunotherapy, radiotherapy, and photodynamic, sonodynamic, chemodynamic, gene, gas, ionic, vascular and magnetothermal therapy. Potential obstacles and perspectives for future research and clinical translation of this new theranostic modality are also discussed.

Nanoparticle-mediated tumor vaccines for personalized therapy: preparing tumor antigens in vivo or ex vivo?

Tumor vaccines, focusing on tailoring individual tumor antigens, have gained much attention in personalized tumor therapy. Recently, breakthroughs have been made in the development of tumor vaccines thanks to the progress in nanotechnology. We will summarize nanoparticle-mediated tumor vaccines for personalized therapy in this review. ROS/heat generating nanoparticles and molecules could induce immunogenic cell death and tumor antigen release in vivo. This strategy often includes chemotherapy, radiotherapy, photodynamic therapy, photothermal therapy, magneto-thermal therapy, etc. On the other hand, ex vivo technologies have been applied for processing of tumor cells/tissues to form effective tumor antigens, in which nanotechnology has shown very good prospects in delivering tumor antigens. In in vivo and ex vivo strategies, nanotechnology also could improve the immune effect through enhancing the uptake by targeting cells, reducing therapeutic drugs/agents, further encapsulating immuno-modulatory molecules or combining with other therapy treatments. Thus, therapeutic vaccines based on nanoparticles have the potential to enhance the immune response and reduce the side effects.

Coordination of injectable self-healing hydrogel with Mn-Zn ferrite@mesoporous silica nanospheres for tumor MR imaging and efficient synergistic magnetothermal-chemo-chemodynamic therapy

Compared to conventional chemotherapy with subcutaneous and intravenous injection, injection of self-healing hydrogel drug-delivery system to tumor site brings less toxicity for normal tissues, but also better specificity for tumor cells on account of spontaneous repair and better retention. More importantly, it is essential to introduce multifunctional nanomaterials into self-healing hydrogel loading chemotherapeutic drugs to significantly enhance tumor treatment effect. Therefore, Rhodamin B isothiocyanate (RBITC)-labeled mesoporous silica nanospheres with Mn-Zn Ferrite (Mn0.6Zn0.4Fe2O4) nanoparticle core (MMSN-RBITC) are prepared and well-dispersed into hydrogel system. The generated heat under alternate magnetic field induces hyperthermia effect for magnetothermal therapy, which could also promote the sensibilization of chemotherapy. Hydroxyl radicals are produced via Fenton-like catalyzation after the cellular uptake of MMSN-RBITCs further promoting the cell apoptosis via chemodynamic therapy. The nanoplatform also presents excellent T2-weighted magnetic resonance imaging contrast enhancement. As a result, the hydrogel system is effectively enhanced and enriched via the introduction of the nanospheres. In vitro and in vivo results indicate that this strategy of self-healing hydrogel loading DOX and MMSN-RBITC can achieve tumor diagnosis and efficiently synergistic magnetothermal-chemo-chemodynamic therapy. This strategy could inspire people to construct more promising platforms combining self-healing hydrogel with multifunctional nanomaterials for more efficient cancer treatment with versatile therapeutic methods.

Thermal-Disrupting Interface Mitigates Intercellular Cohesion Loss for Accurate Topical Antibacterial Therapy.

Bacterial infections remain a leading threat to global health because of the misuse of antibiotics and the rise in drug-resistant pathogens. Although several strategies such as photothermal therapy and magneto-thermal therapy can suppress bacterial infections, excessive heat often damages host cells and lengthens the healing time. Here, a localized thermal managing strategy, thermal-disrupting interface induced mitigation (TRIM), is reported, to minimize intercellular cohesion loss for accurate antibacterial therapy. The TRIM dressing film is composed of alternative microscale arrangement of heat-responsive hydrogel regions and mechanical support regions, which enables the surface microtopography to have a significant effect on disrupting bacterial colonization upon infrared irradiation. The regulation of the interfacial contact to the attached skin confines the produced heat and minimizes the risk of skin damage during thermoablation. Quantitative mechanobiology studies demonstrate the TRIM dressing film with a critical dimension for surface features plays a critical role in maintaining intercellular cohesion of the epidermis during photothermal therapy. Finally, endowing wound dressing with the TRIM effect via in vivo studies in S. aureus infected mice demonstrates a promising strategy for mitigating the side effects of photothermal therapy against a wide spectrum of bacterial infections, promoting future biointerface design for antibacterial therapy.

Graphene Oxide-Grafted Magnetic Nanorings Mediated Magnetothermodynamic Therapy Favoring Reactive Oxygen Species-Related Immune Response for Enhanced Antitumor Efficacy.

In this study, a magnetothermodynamic (MTD) therapy is introduced as an efficient systemic cancer treatment, by combining the magnetothermal effect and the reactive oxygen species (ROS)-related immunologic effect, in order to overcome the obstacle of limited therapeutic efficacy in current magnetothermal therapy (MTT). This approach was achieved by the development of an elaborate ferrimagnetic vortex-domain iron oxide nanoring and graphene oxide (FVIOs-GO) hybrid nanoparticle as the efficient MTD agent. Such a FVIOs-GO nanoplatform was shown to have high thermal conversion efficiency, and it was further proved to generate a significantly amplified ROS level under an alternating magnetic field (AMF). Both in vitro and in vivo results revealed that amplified ROS generation was the dominant factor in provoking a strong immune response at a physiological tolerable temperature below 40 °C in a hypoxic tumor microenvironment. This was supported by the exposure of calreticulin (CRT) on 83% of the 4T1 breast cancer cell surface, direct promotion of macrophage polarization to pro-inflammatory M1 phenotypes, and further elevation of tumor-infiltrating T lymphocytes. As a result of the dual action of magnetothermal effect and ROS-related immunologic effect, impressive in vivo systemic therapeutic efficacy was attained at a low dosage of 3 mg Fe/kg with two AMF treatments, as compared to that of MTT (high dosage of 6-18 mg/kg under four to eight AMF treatments). The MTD therapy reported here has highlighted the inadequacy of conventional MTT that solely relies on the heating effect of the MNPs. Thus, by employing a ROS-mediated immunologic effect, future cancer magnetotherapies can be designed with greatly improved antitumor capabilities.

A Composite of Hyaluronic Acid-Modified Graphene Oxide and Iron Oxide Nanoparticles for Targeted Drug Delivery and Magnetothermal Therapy.

Graphene oxide (GO) nanoparticles have been developed for a variety of biomedical applications as a number of different therapeutic modalities may be added onto them. Here, we report the development and testing of such a multifunctional GO nanoparticle platform that contains a grafted cell-targeting functionality, active pharmaceutical ingredients, and particulates that enable the use of magnetothermal therapy. Specifically, we demonstrate the ability to covalently attach hyaluronic acid (HA) onto GO, and the resultant nanoparticulates (GO-HA) exhibited low inherent toxicity toward two different breast cancer cell lines, BT-474 and MDA-MB-231. Doxorubicin (Dox) and paclitaxel (Ptx) were successfully loaded onto GO-HA with high and moderate efficiencies, respectively. A GO-HA-Dox/Ptx system was significantly better than the GO-Dox/Ptx system at specifically killing CD44-expressing MDA-MB-231 cells but not BT-474 cells that do not express CD44. Further, modified iron oxide nanoparticles were loaded onto the GO-HA-Dox system, enabling the use of magnetic hyperthermia. Hyperthermia in combination with Dox treatment through the GO-HA system showed significantly better performance in reducing viable tumor cell numbers when compared to the individual systems. In summary, we showcase a multifunctional GO nanoparticle system that demonstrates improved efficacy in killing tumor cells.

Progress in Remotely Triggered Hybrid Nanostructures for Next-Generation Brain Cancer Theranostics.

Progress in nanomedicine has enabled the development of smart hybrid nanostructures (HNSs) for brain cancer theranostics, a novel platform that can diagnose the brain while concurrently beginning primary treatment, initiating secondary treatments where necessary, and monitoring the therapy response. These HNSs can release guest molecules/cargoes directly to brain tumors in response to external physical stimuli. Such physical stimulation is generally referred to as remote stimuli which can be externally applied examples include alternating magnetic field, visible or near-infrared light, ultrasound radiation, X-ray, and radiofrequency. The release of therapeutic cargoes in response to physical stimuli can be performed along with photodynamic therapy, photothermal therapy, phototriggered chemotherapeutics, sonodynamic therapy, electrothermal therapy, and magnetothermal therapy. Herein, we review different HNSs currently used as remotely triggered modalities in brain cancer, such as organic-inorganic HNSs, polymer micelles, and liposomes HNSs. We also summarize underlying mechanisms of remote triggering brain cancer therapeutics including single- and two-photon triggering, thermoresponsive HNSs, photoresponsive HNSs, magnetoresponsive HNSs, and electrically and ultrasound-stimulated HNSs. In addition to a brief synopsis of ongoing research progress on "smart" HNSs-based platforms of novel brain cancer therapeutics, the review offers an up-to-date development in this field for neuro-oncologists, material/nanoscientists, and radiologists so that a rapid clinical impact can be achieved through a convergence of multidisciplinary expertise.

Remote Magnetic Control of Autophagy in Mouse B-Lymphoma Cells with Iron Oxide Nanoparticles.

Autophagy is the spontaneous degradation of intracellular proteins and organelles in response to nutrient deprivation. The phagocytosis of iron oxide nanoparticles (IONPs) results in intracellular degradation that can be exploited for use in cancer treatment. Non-invasive magnetic control has emerged as an important technology, with breakthroughs achieved in areas such as magneto-thermal therapy and drug delivery. This study aimed to regulate autophagy in mouse B-lymphoma cells (A20) through the incorporation of IONPs–quantum dots (QDs). We hypothesized that with the application of an external magnetic field after phagocytosis of IONPs–QDs, autophagy of intracellular IONPs–QDs could be regulated in a non-invasive manner and subsequently modulate the regulation of inflammatory responses. The potential of this approach as a cancer treatment method was explored. The application of IONPs and an external magnetic force enabled the non-invasive regulation of cell autophagy and modulation of the self-regulatory function of cells. The combination of non-invasive magnetic fields and nanotechnology could provide a new approach to cancer treatment.

Synthesis and Characterization of Tb‐Doped Nanoferrites

AbstractTb3+‐substituted superparamagnetic iron‐oxide‐based nanoparticles (NPs) that can be promising for possible multimodal drug carrier and radiotherapy are presented. These NPs were obtained using a reverse micelle template method with controlled micelle size. The atomic ratio of Tb/Fe ions was found to be very close to that expected from the stoichiometry of the reagents used. Aqueous suspensions of Tb‐doped nanoferrites are emissive with emission peaks characteristic for the Tb3+ dopant. Time‐resolved fluorescence decay data revealed two populations occupying inequivalent matrix sites. Above 80 K the Tb‐doped nanoferrites were superparamagnetic, which is a prerequisite for their use as carriers in magnetic‐field‐driven targeted therapies. The incorporation of up to 15 at.% of Tb3+ in their core resulted in a decrease of magnetization. Nevertheless, this magnetization appears to be sufficient for their use as carriers in an external magnetic field, and, of equal importance, stable isotope 159Tb3+ could be replaced by radioactive 161Tb3+, yielding multimodal NPs, suitable for conjugated therapies such as radiotherapy and magnetothermal therapy, as well as targeted drug delivery.

Enhanced Targeted Delivery of Cyclodextrin-Based Supermolecules by Core-Shell Nanocapsules for Magnetothermal Chemotherapy.

In this study, double-emulsion capsules (DECs) capable of concealing drug-incorporated targeted-supermolecules are developed to achieve "on-demand" supermolecule release and enhanced sequential targeting for magneto-chemotherapy. These water-in-oil-in-water DECs less than 200 nm in diameter are synthesized using a single component of PVA (polyvinyl alcohol) polymer and the magnetic nanoparticles, which are capable of encapsulating large quantities of targeted supermolecules composed of palitaxel-incorporated beta-cyclodextrin decorated by hyaluronic acid (HA, a CD44-targeting ligand) in the watery core. The release profiles (slow, sustained and burst release) of the targeted supermolecules can be directly controlled by regulating the high-frequency magnetic field (HFMF) and polymer conformation without sacrificing the targeting ability. Through an intravenous injection, the positive targeting of the supermolecules exhibited a 20-fold increase in tumor accumulation via the passive targeting and delivery of DECs followed by positive targeting of the supermolecules. Moreover, this dual-targeting drug-incorporated supermolecular delivery vehicle at the tumor site combined with magneto-thermal therapy suppressed the cancer growth more efficiently than treatment with either drug or supermolecule alone.