Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells.

PURPOSE: Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms. METHODS: We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors. RESULTS: Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups. CONCLUSION: MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.

Ultrasound Image Temperature Monitoring Based on a Temporal-Informed Neural Network.

Real-time and accurate temperature monitoring during microwave hyperthermia (MH) remains a critical challenge for ensuring treatment efficacy and patient safety. This study presents a novel approach to simulate real MH and precisely determine the temperature of the target region within biological tissues using a temporal-informed neural network. We conducted MH experiments on 30 sets of phantoms and 10 sets of ex vivo pork tissues. We proposed a novel perspective: the evolving tissue responses to continuous electromagnetic radiation stimulation are a joint evolution in temporal and spatial dimensions. Our model leverages TimesNet to extract periodic features and Cloblock to capture global information relevance in two-dimensional periodic vectors from ultrasound images. By assimilating more ultrasound temporal data, our model improves temperature-estimation accuracy. In the temperature range 25-65 °C, our neural network achieved temperature-estimation root mean squared errors of approximately 0.886 °C and 0.419 °C for fresh ex vivo pork tissue and phantoms, respectively. The proposed temporal-informed neural network has a modest parameter count, rendering it suitable for deployment on ultrasound mobile devices. Furthermore, it achieves temperature accuracy close to that prescribed by clinical standards, making it effective for non-destructive temperature monitoring during MH of biological tissues.

Broadband microwave spiral applicator (105-125 MHz) for in vitro examinations of hyperthermia-induced tumor cell death forms - first analyses with human breast cancer cells.

PURPOSE: Local tumor heating with microwave applicators has been used in multimodal breast cancer therapies. This hyperthermia allows to target small regions while marginally affecting healthy tissue. However, most preclinical examinations only use simplified heating methods. Microwave applicators employed for deep heating to provide the greatest depth of penetration operate in the tens to hundreds frequency. Therefore, we aimed to adapt and test a clinically often used broadband spiral applicator (105-125 MHz) for hyperthermia with clinically wanted temperatures of 41 and 44 °C in in vitro settings with human breast cancer cell lines and with simulations. MATERIAL AND METHODS: A clinically used spiral-microwave applicator (105-125 MHz) was the basis for the construction, simulation, and optimization of the in vitro HT set-up under stationary conditions. Microwave effects on tumor cell death of two human breast cancer cell lines (hormone-receptor positive MCF-7 and triple-negative MDA-MB-231) were compared with conventional heating in a contact-heating chamber. Cell death forms were analyzed by AnnexinV/Propidium iodide staining. RESULTS: An in vitro spiral applicator microwave-based heating system that is effective at applying heat directly to adherent breast cancer cells in cell culture flasks with medium was developed. Simulations with COMSOL proved appropriate heat delivery and an optimal energy coupling at a frequency of 111 ± 2.5 MHz. Apoptosis and necrosis induction and significantly higher cell death rates than conventional heating at both temperatures were observed, and MCF-7 showed higher death rates than MDA-MB-231 tumor cells. CONCLUSIONS: Well-characterized in vitro heating systems are mandatory for a better understanding of the biological effects of hyperthermia in tumor therapies and to finally determine optimized clinical treatment schemes.

Comparison of Microwave Hyperthermia Applicator Designs with Fora Dipole and Connected Array.

In microwave hyperthermia tumor therapy, electromagnetic waves focus energy on the tumor to elevate the temperature above its normal levels with minimal injury to the surrounding healthy tissue. Microwave hyperthermia applicator design is important for the effectiveness of the therapy and the feasibility of real-time application. In this study, the potential of using fractal octagonal ring antenna elements as a dipole antenna array and as a connected array at 2.45 GHz for breast tumor hyperthermia application was investigated. Microwave hyperthermia treatment models consisting of different fractal octagonal ring antenna array designs and a breast phantom are simulated in COMSOL Multiphysics to obtain the field distributions. The antenna excitation phases and magnitudes are optimized using the global particle swarm algorithm to selectively increase the specific absorption rate at the target region while minimizing hot spots in other regions within the breast. Specific absorption rate distributions, obtained inside the phantom, are analyzed for each proposed microwave hyperthermia applicator design. The dipole fractal octagonal ring antenna arrays are comparatively assessed for three different designs: circular, linear, and Cross-array. The 16-antenna dipole array performance was superior for all three 1-layer applicator designs, and no distinct difference was found between 16-antenna circular, linear, or cross arrays. Two-layer dipole arrays have better performance in the deep-tissue targets than one-layer arrays. The performance of the connected array with a higher number of layers exceeds the performance of the dipole arrays in the superficial regions, while they are comparable for deep regions of the breast. The 1-layer 12-antenna circular FORA dipole array feasibility as a microwave hyperthermia applicator was experimentally shown.

Metamaterial based AMC backed archimedean spiral antenna for in-vitro microwave hyperthermia of skin cancer.

This research article presents a study that uses microwave frequencies (ISM band) for treatment of skin cancer by heating the malignant cells on skin with a Microwave Hyperthermia (MWHT) applicator. The proposed MWHT applicator has been designed as an Archimedean Spiral Microstrip Patch Antenna (AMSPA) of dimensions 38 × 38 × 1.64 mm3 backed with a Meshed-shaped AMC (48 × 48 × 3.27mm3) reflector, placed at an optimized distance of 12 mm from AMSPA. The proposed AMSPA is designed as a single spiral resonator and fabricated on FR-4 substrate, excited using a feed network. The proposed AMSPA shows a resonance at 2.5 GHz with an impedance BW of 260 MHz (2.37-2.63 GHz) and peak gain of 3.20 dB with a bidirectional radiation pattern. An AMC is placed at its backside that can be exploited as a phase-compensation surface to attain an in-phase profile for directive emission and improve the BW upto 470 MHz, peak gain to 6.8 dB and also enhance the front-to-back ratio of the radiating antenna with radiation efficiency of 80%. The simulated environment for hyperthermia analysis is set up using penne's Bio-Heat equations to deliver microwave energy to the bio-mimic, that leads to a rise in temperature over the designed bio-mimic in CST MWS in the range of 41-45°C. The validation of MWHT radiation properties and temperature rise inside the malignancy of phantom is carried out by fabricating the bio-mimic using gelatine, vegetable oils and glycerol. This set up enhances the penetration-depth of EM waves inside the tri-layered phantom up-to 29.5 mm with Effective Field Surface of 36 × 36 mm2 and SAR of 8 W/Kg.

This article discusses the design and development of a device designed to treat skin cancer, specifically melanoma. This device is called a Microwave Hyperthermia (MWHT) applicator. The applicator sends out focused waves of microwave energy but at a specific frequency of ISM band. These waves heat up a model of human skin, simulating what would happen if this is used on a real person with cancer. The goal is to heat the cancer to around 45°C, which can help treat it. The special thing about this applicator is that it's designed to be very compact and have good gain. It heats up the cancer without causing harm to the healthy tissues nearby. The researchers tested it extensively and found that it works well. It has a wide range of effectiveness for different tumor sizes and depths within the skin. To make sure it is safe and accurate, a model of a human forearm using materials like gelatin and water has been prepared. Then used the applicator on this model and measured the temperature increase. After about 40 minutes of exposure, there is a temperature rise of about 45 degrees Celsius. Thus this article is about a device that uses special waves to heat up and treat skin cancer. It's designed to be safe and effective, and the tests show it works on a model of human skin. This could be a useful tool for treating skin cancer in the future.

Microwave Hyperthermia of Brain Tumors: A 2D Assessment Parametric Numerical Study.

Due to the clinically proven benefit of hyperthermia treatments if added to standard cancer therapies for various tumor sites and the recent development of non-invasive temperature measurements using magnetic resonance systems, the hyperthermia community is convinced that it is a time when even patients with brain tumors could benefit from regional microwave hyperthermia, even if they are the subject of a treatment to a vital organ. The purpose of this study was to numerically analyze the ability to achieve a therapeutically relevant constructive superposition of electromagnetic (EM) waves in the treatment of hyperthermia targets within the brain. We evaluated the effect of the target size and position, operating frequency, and the number of antenna elements forming the phased array applicator on the treatment quality. In total, 10 anatomically realistic 2D human head models were considered, in which 10 circular hyperthermia targets with diameters of 20, 25, and 30 mm were examined. Additionally, applicators with 8, 12, 16, and 24 antenna elements and operating frequencies of 434, 650, 915, and 1150 MHz, respectively, were analyzed. For all scenarios considered (4800 combinations), the EM field distributions of individual antenna elements were calculated and treatment planning was performed. Their quality was evaluated using parameters applied in clinical practice, i.e., target coverage (TC) and the target to hot-spot quotient (THQ). The 12-antenna phased array system operating at 434 MHz was the best candidate among all tested systems for HT treatments of glioblastoma tumors. The 12 antenna elements met all the requirements to cover the entire target area; an additional increase in the number of antenna elements did not have a significant effect on the treatment quality.

Antenna Excitation Optimization with Deep Learning for Microwave Breast Cancer Hyperthermia.

Microwave hyperthermia (MH) requires the effective calibration of antenna excitations for the selective focusing of the microwave energy on the target region, with a nominal effect on the surrounding tissue. To this end, many different antenna calibration methods, such as optimization techniques and look-up tables, have been proposed in the literature. These optimization procedures, however, do not consider the whole nature of the electric field, which is a complex vector field; instead, it is simplified to a real and scalar field component. Furthermore, most of the approaches in the literature are system-specific, limiting the applicability of the proposed methods to specific configurations. In this paper, we propose an antenna excitation optimization scheme applicable to a variety of configurations and present the results of a convolutional neural network (CNN)-based approach for two different configurations. The data set for CNN training is collected by superposing the information obtained from individual antenna elements. The results of the CNN models outperform the look-up table results. The proposed approach is promising, as the phase-only optimization and phase-power-combined optimization show a 27% and 4% lower hotspot-to-target energy ratio, respectively, than the look-up table results for the linear MH applicator. The proposed deep-learning-based optimization technique can be utilized as a protocol to be applied on any MH applicator for the optimization of the antenna excitations, as well as for a comparison of MH applicators.

Tumour shape-dependent microwave hyperthermia using a novel coaxial micro-cut slot antenna.

Given that the effectiveness of interstitial hyperthermia for cancer treatment is related to the temperature achieved during the ablation process, there is a need for an accurate understanding of the required temperature distribution which is affected by the physical shape and form of tumours. Although a maximum peak temperature value and minimum backward heating are desired, the temperature distribution needs to be not only high but also uniformly extended over a section instead of at one peak point, especially when a roughly oval-shaped tumour is aligned with the antenna. In this case, achieving a high temperature peak destroys only the central cancerous cells after the first minutes of ablation, leaving the cells on the side alive. In this paper, a complex model was extended for the study of the heat distribution of an antenna over a porous liver composed of blood, cancerous cells, and normal tissue. Three different types of antenna were analysed: single-slot, double-slot, and dipole-tip. A novel structure made up of the single-slot antenna with a micron cut, named the micro-cut slot (MCS) antenna, was proposed and analysed. Thanks to the new structure, high uniform temperature distribution with minimum backward heating was achieved. The extended model equations, which encompass a coupled nonlinear set of transient Maxwell's electromagnetic equations, extended Darcy-Brinkman equation, and local thermal non-equilibrium equations for porous medium approximation, were solved numerically using the novel alternating direction implicit, finite-difference time-domain approach. The results showed that each type of antenna could be useful if chosen according to the shape of the tumour. In comparison with previously used antennas, the MCS antenna presented a good combination of the required goals of achieving uniform high temperature distribution and minimum backward heating.

An integrated platform for small-animal hyperthermia investigations under ultra-high-field MRI guidance.

PURPOSE: Integrating small-animal experimental hyperthermia instrumentation with magnetic resonance imaging (MRI) affords real-time monitoring of spatial temperature profiles. This study reports on the development and preliminary in vivo characterisation of a 2.45 GHz microwave hyperthermia system for pre-clinical small animal investigations, integrated within a 14 T ultra-high-field MRI scanner. MATERIALS AND METHODS: The presented system incorporates a 3.5 mm (OD) directional microwave hyperthermia antenna, positioned adjacent to the small-animal target, radiating microwave energy for localised heating of subcutaneous tumours. The applicator is integrated within the 30 mm bore of the MRI system. 3D electromagnetic and biothermal simulations were implemented to characterise hyperthermia profiles from the directional microwave antenna. Experiments in tissue mimicking phantoms were performed to assess hyperthermia profiles and validate MR thermometry against fibre-optic temperature measurements. The feasibility of delivering in vivo hyperthermia exposures to subcutaneous 4T1 tumours in experimental mice under simultaneous MR thermometry guidance was assessed. RESULTS: Simulations and experiments in tissue mimicking phantoms demonstrated the feasibility of heating 21-982 mm3 targets with 8-12 W input power. Minimal susceptibility and electrical artefacts introduced by the hyperthermia applicator were observed on MR imaging. MR thermometry was in excellent agreement with fibre-optic temperatures measurements (max. discrepancy ≤0.6 °C). Heating experiments with the reported system demonstrated the feasibility of heating subcutaneous tumours in vivo with simultaneous MR thermometry. CONCLUSIONS: A platform for small-animal hyperthermia investigations under ultra-high-field MR thermometry was developed and applied to heating subcutaneous tumours in vivo.

Design and characterisation of a phased antenna array for intact breast hyperthermia.

PURPOSE: Currently available hyperthermia technology is not well suited to treating cancer malignancies in the intact breast. This study investigates a microwave applicator incorporating multiple patch antennas, with the goal of facilitating controllable power deposition profiles for treating lesions at diverse locations within the intact breast. MATERIALS AND METHODS: A 3D-computational model was implemented to assess power deposition profiles with 915 MHz applicators incorporating a hemispheric groundplane and configurations of 2, 4, 8, 12, 16 and 20 antennas. Hemispheric breast models of 90 mm and 150 mm diameter were considered, where cuboid target volumes of 10 mm edge length (1 cm3) and 30 mm edge length (27 cm3) were positioned at the centre of the breast, and also located 15 mm from the chest wall. The average power absorption (αPA) ratio expressed as the ratio of the PA in the target volume and in the full breast was evaluated. A 4-antenna proof-of-concept array was fabricated and experimentally evaluated. RESULTS: Computational models identified an optimal inter-antenna spacing of 22.5° along the applicator circumference. Applicators with 8 and 12 antennas excited with constant phase presented the highest αPA at centrally located and deep-seated targets, respectively. Experimental measurements with a 4-antenna proof-of-concept array illustrated the potential for electrically steering power deposition profiles by adjusting the relative phase of the signal at antenna inputs. CONCLUSIONS: Computational models and experimental results suggest that the proposed applicator may have potential for delivering conformal thermal therapy in the intact breast.

Interstitial microwave treatment for cancer: historical basis and current techniques in antenna design and performance.

The use of microwaves (MW) for thermal cancer treatment began in the late 1970s. At first, hyperthermia was induced by using single antennas applied interstitially. This was followed by arrays of multiple interstitial antennas driven synchronously at 915 or 2450 MHz. This early work focused on hyperthermia as an adjuvant therapy, but more recently has evolved into a thermally ablative monotherapy. Increased power required to thermally ablate tissues required additional developments such as internally cooled antennas. Larger tumours have also been ablated with MW antenna arrays activated synchronously or non-synchronously. Numerical modelling has provided clinical treatment planning guidance and device design insight throughout this history. MW thermal therapy systems, treatment planning, navigation and image guidance continue to evolve to provide better tools and options for clinicians and patients in order to provide targeting optimisation with the goal of improved treatment for the patient and durable cancer eradication. This paper reviews the history and related technological developments, including antenna design, of MW heating for both hyperthermia and ablation.

Design of a compact antenna with flared groundplane for a wearable breast hyperthermia system.

PURPOSE: Currently available microwave hyperthermia systems for breast cancer treatment do not conform to the intact breast and provide limited control of heating patterns, thereby hindering an effective treatment. A compact patch antenna with a flared groundplane that may be integrated within a wearable hyperthermia system for the treatment of the intact breast disease is proposed. MATERIALS AND METHODS: A 3D simulation-based approach was employed to optimise the antenna design with the objective of maximising the hyperthermia treatment volume (41 °C iso-therm) while maintaining good impedance matching. The optimised antenna design was fabricated and experimentally evaluated with ex vivo tissue measurements. RESULTS: The optimised compact antenna yielded a -10 dB bandwidth of 90 MHz centred at 915 MHz, and was capable of creating hyperthermia treatment volumes up to 14.4 cm(3) (31 mm × 28 mm × 32 mm) with an input power of 15 W. Experimentally measured reflection coefficient and transient temperature profiles were in good agreement with simulated profiles. Variations of + 50% in blood perfusion yielded variations in the treatment volume up to 11.5%. When compared to an antenna with a similar patch element employing a conventional rectangular groundplane, the antenna with flared groundplane afforded 22.3% reduction in required power levels to reach the same temperature, and yielded 2.4 times larger treatment volumes. CONCLUSION: The proposed patch antenna with a flared groundplane may be integrated within a wearable applicator for hyperthermia treatment of intact breast targets and has the potential to improve efficiency, increase patient comfort, and ultimately clinical outcomes.

A two-stage exacerbated hypoxia nanoengineering strategy induced amplifying activation of tirapazamine for microwave hyperthermia-chemotherapy of breast cancer.

Microwave hyperthermia (MH) is an emerging treatment for solid tumors, such as breast cancer, due to its advantages of minimally invasive and deep tissue penetration. However, MH induced tumor hypoxia is still an obstacle to breast tumor treatment failure. Therefore, an original nanoengineering strategy was proposed to exacerbate hypoxia in two stages, thereby amplifying the efficiency of activating tirapazamine (TPZ). And a novel microwave-sensitized nanomaterial (GdEuMOF@TPZ, GEMT) is designed. GdEuMOF (GEM) nanoparticles are certified excellent microwave (MW) sensitization performance, thus improving tumor selectivity to achieve MH. Meanwhile MW can aggravate the generation of thrombus and caused local circulatory disturbance of tumor, resulting in the Stage I exacerbated hypoxia environment passively. Due to tumor heterogeneity and uneven hypoxia, GEMT nanoparticles under microwave could actively deplete residual oxygen through the chemical reaction, exacerbating hypoxia level more evenly, thus forming the Stage II of exacerbated hypoxia environment. Consequently, a two-stage exacerbated hypoxia GEMT nanoparticles realize amplifying activation of TPZ, significantly enhance the efficacy of microwave hyperthermia and chemotherapy, and effectively inhibit breast cancer. This research provides insights into the development of progressive nanoengineering strategies for effective breast tumor therapy.

PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy.

Hypoxia is typically the leading cause of radiotherapy (RT) resistance in solid tumors, and glutathione (GSH) overexpression in tumor cells is a potent antioxidant mechanism that protects tumor cells from radiation damage. Herein, we developed a sorafenib (SFN) loaded-PLGA hydrogel system (SPH) in combination with microwave (MW) hyperthermia for RT sensitization. SPH with stable properties was produced by combining SFN and PLGA in a specific ratio and encapsulating the mixture in agarose hydrogel. Intratumoral injection of SPH to mice combined with MW hyperthermia can not only directly cause thermal damage to tumor cells, but also increase blood oxygen delivery to the tumor site, thus overcoming the problem of intratumoral hypoxia and achieving "first layer" RT sensitization. Moreover, high temperatures can cause the hydrogel to disintegrate and release SFN. Not only can SFN inhibit tumor growth, but it can also achieve the "second layer" of RT sensitization by inhibiting glutathione (GSH) synthesis in cells and increasing reactive oxygen species (ROS) production. Experiments, both in vitro and in vivo, have indicated that SPH and MW hyperthermia can achieve a double RT sensitization effect and a significant tumor inhibition effect. In conclusion, combining our SPH nanosystem and thermoradiotherapy is a promising anti-tumor treatment.

Microwave hyperthermia represses human papillomavirus oncoprotein activity and induces cell death due to cell stress in 3D tissue models of anogenital precancers and cancers.

BACKGROUND: Hyperthermia is a well-accepted cancer therapy. Microwaves provide a very precise, targeted means of hyperthermia and are currently used to treat plantar warts caused by cutaneous-infective human papillomaviruses (HPVs). Other HPV genotypes infecting the anogenital mucosa cause genital warts or preneoplastic lesions or cervical cancer. Effective, non-ablative therapies for these morbid HPV-associated lesions are lacking. METHODS: The molecular consequences of microwave treatment were investigated in in vitro cultured three-dimensional HPV-positive cervical tumour tissues, and tissues formed from HPV-infected normal immortalised keratinocytes. Microwave energy delivery to tissues was quantified. Quantitative reverse transcriptase PCR was used to quantify mRNA expression. Immunohistochemistry and fluorescence immunostaining was used to assess protein expression. FINDINGS: Microwave energy deposition induced sustained, localised cell death at the treatment site. There was a downregulation in levels of HPV oncoproteins E6 and E7 alongside a reduction in cellular growth/proliferation and induction of apoptosis/autophagy. HSP70 expression confirmed hyperthermia, concomitant with induction of translational stress. INTERPRETATION: The data suggest that microwave treatment inhibits tumour cell proliferation and allows the natural apoptosis of HPV-infected cells to resume. Precision microwave delivery presents a potential new treatment for treating HPV-positive anogenital precancerous lesions and cancers. FUNDING: Funding was through an Innovate UK Biomedical Catalyst grant (ID# 92138-556187), a Chief Scientist Office grant (TCS/19/11) and core support from Medical Research Council (MC_ UU_12014) core funding for the MRC-University of Glasgow Centre for Virus Research.

Shikonin-Loaded Hollow Fe-MOF Nanoparticles for Enhanced Microwave Thermal Therapy.

Microwave (MW) thermal therapy has been widely used for the treatment of cancer in clinics, but it still shows limited efficacy and a high recurrence rate owing to non-selective heat delivery and thermo-resistance. Regulating glycolysis shows great promise to improve MW thermal therapy since glycolysis plays an important role in thermo-resistance, progression, metabolism, and recurrence. Herein, we developed a delivery nanosystem of shikonin (SK)-loaded and hyaluronic acid (HA)-modified hollow Fe-MOF (HFM), HFM@SK@HA, as an efficient glycolysis-meditated agent to improve the efficacy of MW thermal therapy. The HFM@SK@HA nanosystem shows a high SK loading capacity of 31.7 wt %. The loaded SK can be effectively released from the HFM@SK@HA under the stimulation of an acidic tumor microenvironment and MW irradiation, overcoming the intrinsically low solubility and severe toxicity of SK. We also find that the HFM@SK@HA can not only greatly improve the heating effect of MW in the tumor site but also mediate MW-enhancing dynamic therapy efficiency by catalyzing the endogenous H2O2 to generate reactive oxygen species (ROS). As such, the MW irradiation treatment in the presence of HFM@SK@HA in vitro enables a highly improved anti-tumor efficacy due to the combined effect of released SK and generated ROS on inhibiting glycolysis in cancer cells. Our in vivo experiments show that the tumor inhibition rate is up to 94.75% ± 3.63% with no obvious recurrence during the 2 weeks after treatment. This work provides a new strategy for improving the efficacy of MW thermal therapy.

ICAM-1 targeted thermal-sensitive micelles loaded with tofacitinib for enhanced treatment of rheumatoid arthritis via microwave assistance.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease without effective treatment. Tofacitinib (TOF) is a JAK inhibitor that can be used for RA therapy, but it still faces the problems of nonspecific distribution and relatively low therapeutic effect. Herein, ICAM-1-modified TOF-loaded P(AN-co-AAm)-PEG micelles (AI-TM) were developed, which can result in an enhanced RA therapy when combining with microwave hyperthermia (MH). It was found that AI-TM could rapidly release the encapsulated TOF under a thermal condition of >43 °C, which was due to the fact that the polymeric micelles has an upper critical solution temperature (UCST) of 43 °C. AI-TM could specifically distribute into the inflamed joints of RA mice, which is associated with the high affinity between anti-ICAM-1 and overexpressed ICAM-1 receptors. Moreover, the combination of AI-TM and MH could result in a remarkably enhanced anti-rheumatic activity, which was related to the RA-targeted ability of AI-TM, the rapid TOF release under MH, and the combined effect between TOF and MH treatment. Our study definitely provides a novel strategy for effective treatment of RA.

The anti-tumor effects of the combination of microwave hyperthermia and lobaplatin against breast cancer cells in vitro and in vivo.

BACKGROUND: Breast cancer is the main lethal disease among females. The combination of lobaplatin and microwave hyperthermia plays a crucial role in several kinds of cancer in the clinic, but its possible mechanism in breast cancer has remained indistinct. METHODS: Mouse models were used to detect breast cancer progression. Cell growth was explored with MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphonyl)-2H-tetrazolium) and colony formation assays. Cell migration and invasion were investigated with a transwell assay. Cell apoptosis was probed with flow cytometry. The expression of apoptosis-associated proteins was examined with Western blots. RESULT: Combination treatment decreased breast cancer cell viability, colony formation, cell invasion and metastasis. In addition, the treatment-induced breast cancer cell apoptosis and autophagy, activated the c-Jun N-terminal kinase (JNK) signaling pathway, suppressed the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, and down-regulated IAP and Bcl-2 family protein expression. CONCLUSION: These results indicate that lobaplatin is an effective breast cancer anti-tumor agent. Microwave hyperthermia was a useful adjunctive treatment. Combination treatment was more efficient than any single therapy. The possible mechanism for this effect was mainly associated with activation of the JNK signaling pathway, inactivation of the AKT/mTOR signaling pathway and down-regulation of the Bcl-2 and IAP families.

Modeling of interstitial microwave hyperthermia for hepatic tumors using floating sleeve antenna.

Microwave hyperthermia is a treatment modality that uses microwaves to destroy cancer cells by increasing their temperature to 41-45 °C. This study aims to design, model, and simulate a microwave sleeve antenna for hepatic (liver) hyperthermia. A floating sleeve antenna with 0.5 w input power was designed to resonate at 2.45 GHz. The antenna was tested in six different 3D liver models. The models were varied from a very simple model without a tumor and blood vessels to complex models that contain realistic tumors and blood vessels. To test the capability of the proposed antenna for heating the interstitial tumors, the size, shape, and location of the tumor were changed. The specific absorption rate (SAR) and temperature were calculated for each model. The tumors' temperature was elevated between 43 and 45 °C, while the temperature of the surrounding tissues was below 41 °C. The Specific Absorption Rate (SAR) was between 29 and 30 W/kg in the tumors and below 24 W/Kg in the surrounding tissues. The return loss of the antenna varied from - 45 to - 25 dB for the six models. The antenna could heat hepatic tumors with different sizes and locations. The heating process was performed in a short time by using a very low input power compared to all previous studies.

Micro-Opening Ridged Waveguide Tumor Hyperthermia Antenna Combined with Microwave-Sensitive MOF Material for Tumor Microwave Hyperthermia Therapy.

Microwave hyperthermia is an emerging minimally invasive therapy in which thermal damage and apoptosis of tumor cells are induced by local heating of tissues with microwave radiation. Recently, microwave hyperthermia has been widely used in clinical practice; however, uneven aggregation and dispersion of malignant tumors after microwave hyperthermia are the main problems associated with this method. In this work, a microridged waveguide tumor hyperthermia antenna with an operating frequency of 915 MHz was designed. Although its volume is only 6.6 cm3, it exhibited a highly focused heating effect, achieving rapid heating in a small area. However, microwave hyperthermia has several shortcomings. Microwaves cannot specifically identify and target tumors; this decreases the efficiency of the treatment if the temperature of the tumor site is not sufficiently high for its size and location. Therefore, Zr metal-organic framework (ZrMOF)-derived composite ZCNC was synthesized using the ultrasonic aerosol flow method, which has good microwave sensitization and biosafety. ZCNC reduced the damage to normal cells and greatly improved the tumor treatment effect of microwave hyperthermia (tumor inhibition rate reached 78.01%). Thus, the proposed strategy effectively improves the current clinical microwave hyperthermia treatment method.