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.

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.

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.

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.

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.

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.

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.

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.

Rotationally Adjustable Hyperthermia Applicators: A Computational Comparative Study of Circular and Linear Array Applicators.

Microwave breast hyperthermia (MH) aims to increase the temperature at the tumor location with minimal change in the healthy tissue. To this end, the specific absorption rate (SAR) inside the breast is optimized. The choice of the MH applicator design is important for a superior energy focus on the target. Although hyperthermia treatment planning (HTP) changes for every patient, the MH applicator is required to be effective for different breast models and tumor types. The linear applicator (LA) is one of the previously proposed applicator designs with linearly arranged antennas; however, it suffers from low focusing ability in certain breast regions due to its unsymmetrical geometrical features. In this paper, we propose to radially adjust the LA to obtain alternative excitation schemes without actually changing the applicator. Antipodal Vivaldi antennas were utilized, and the antenna excitations were optimized with particle swarm optimization (PSO). The comparison of the rotated and the fixed linear applicator, between 12-antenna circular and linear applicators, and finally, between a 24-antenna circular applicator are provided. Within the 12 rotation angles and two target locations that were analyzed, the 135° axially rotated linear applicator gave a 35% to 84% higher target-to-breast SAR ratio (TBRS) and a 21% to 28% higher target-to-breast temperature ratio (TBRT) than the fixed linear applicator. For the deep-seated target, the 135° rotated linear applicator had an 80% higher TBRS and a 59% higher TBRT than the 12-antenna circular applicator, while the results were comparable to the 24-antenna circular applicator.

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.

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.

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.

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.

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.

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.

Experimental Validation of the MRcollar: An MR Compatible Applicator for Deep Heating in the Head and Neck Region.

Clinical effectiveness of hyperthermia treatments, in which tumor tissue is artificially heated to 40-44 °C for 60-90 min, can be hampered by a lack of accurate temperature monitoring. The need for noninvasive temperature monitoring in the head and neck region (H&N) and the potential of MR thermometry prompt us to design an MR compatible hyperthermia applicator: the MRcollar. In this work, we validate the design, numerical model, and MR performance of the MRcollar. The MRcollar antennas have low reflection coefficients (<-15 dB) and the intended low interaction between the individual antenna modules (<-32 dB). A 10 °C increase in 3 min was reached in a muscle-equivalent phantom, such that the specifications from the European Society for Hyperthermic Oncology were easily reached. The MRcollar had a minimal effect on MR image quality and a five-fold improvement in SNR was achieved using the integrated coils of the MRcollar, compared to the body coil. The feasibility of using the MRcollar in an MR environment was shown by a synchronous heating experiment. The match between the predicted SAR and measured SAR using MR thermometry satisfied the gamma criteria [distance-to-agreement = 5 mm, dose-difference = 7%]. All experiments combined show that the MRcollar delivers on the needs for MR-hyperthermia in the H&N and is ready for in vivo investigation.

Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy.

This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have confirmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and ensuing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave antenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.

Suitability of eigenvalue beam-forming for discrete multi-frequency hyperthermia treatment planning.

PURPOSE: Thermal dose delivery in microwave hyperthermia for cancer treatment is expected to benefit from the introduction of ultra-wideband (UWB)-phased array applicators. A full exploitation of the combination of different frequencies to improve the deposition pattern is, however, a nontrivial problem. It is unclear whether the cost functions used for hyperthermia treatment planning (HTP) optimization in the single-frequency setting can be meaningfully extended to the UWB case. METHOD: We discuss the ability of the eigenvalue (EV) and a novel implementation of iterative-EV (i-EV) beam-forming methods to fully exploit the available frequency spectrum when a discrete set of simultaneous operating frequencies is available for treatment. We show that the quadratic power deposition ratio solved by the methods can be maximized by only one frequency in the set, therefore rendering EV inadequate for UWB treatment planning. We further investigate whether this represents a limitation in two realistic test cases, comparing the thermal distributions resulting from EV and i-EV to those obtained by optimizing for other nonlinear cost functions that allow for multi-frequency. RESULTS: The classical EV-based single-frequency HTP yields systematically lower target SAR deposition and temperature values than nonlinear HTP. In a larynx target, the proposed single-frequency i-EV scheme is able to compensate for this and reach temperatures comparable to those given by global nonlinear optimization. In a meninges target, the multi-frequency setting outperforms the single-frequency one, achieving better target coverage and 0 . 5 ∘ C higher T 90 in the tumor than single-frequency-based HTP. CONCLUSIONS: Classical EV performs poorly in terms of resulting target temperatures. The proposed single-frequency i-EV scheme can be a viable option depending on the patient and tumor to be treated, as long as the proper operating frequency can be selected across a UWB range. Multi-frequency HTP can bring a considerable benefit in regions typically difficult to treat such as the brain.

Efficient focusing of microwave hyperthermia for small deep-seated breast tumors treatment using particle swarm optimization.

Focused microwave hyperthermia is a technique with advantage of high accuracy and low side effects for breast tumor treatments. In this study, an efficient focusing technique for noninvasive microwave hyperthermia treatment for breast tumors is presented. Particle Swarm Optimization (PSO) is used to find the optimum excitations (phases and amplitudes) of a three dimension (3D) Micro-Strip Patch (MSP) antenna array operating at 2.45 GHz. The antenna excitations are optimized to maximize the power loss density and the Specific Absorption Rate (SAR) at the tumor location, to reach the required hyperthermia temperature (above 42 °C) at the tumor location without causing hot spots in healthy tissues. The technique is tested on a challenging scenario of a 3D realistic breast model having a tumor less than 1 cm3 volume and embedded in different locations deep in the glandular tissue of a very dense breast. The results confirmed the capability of the focusing technique.

MoS2-based nanocomposites for cancer diagnosis and therapy.

Molybdenum is a trace dietary element necessary for the survival of humans. Some molybdenum-bearing enzymes are involved in key metabolic activities in the human body (such as xanthine oxidase, aldehyde oxidase and sulfite oxidase). Many molybdenum-based compounds have been widely used in biomedical research. Especially, MoS2-nanomaterials have attracted more attention in cancer diagnosis and treatment recently because of their unique physical and chemical properties. MoS2 can adsorb various biomolecules and drug molecules via covalent or non-covalent interactions because it is easy to modify and possess a high specific surface area, improving its tumor targeting and colloidal stability, as well as accuracy and sensitivity for detecting specific biomarkers. At the same time, in the near-infrared (NIR) window, MoS2 has excellent optical absorption and prominent photothermal conversion efficiency, which can achieve NIR-based phototherapy and NIR-responsive controlled drug-release. Significantly, the modified MoS2-nanocomposite can specifically respond to the tumor microenvironment, leading to drug accumulation in the tumor site increased, reducing its side effects on non-cancerous tissues, and improved therapeutic effect. In this review, we introduced the latest developments of MoS2-nanocomposites in cancer diagnosis and therapy, mainly focusing on biosensors, bioimaging, chemotherapy, phototherapy, microwave hyperthermia, and combination therapy. Furthermore, we also discuss the current challenges and prospects of MoS2-nanocomposites in cancer treatment.